Disease manifestations are determined by both virus and host factors. The disease remains asymptomatic in 10% to 60% of cases, while others develop a combination of sore throat, cough, myalgia, fever, dyspnea, fatigue, headache, anosmia, and ageusia. Although COVID-19 primarily affects the respiratory system, the virus can involve multiple organs including kidneys.

Kidney involvement in patients with COVID-19 may manifest as isolated urinary abnormalities, such as hematuria and/or proteinuria, AKI, or GN. In initial studies, the incidence of AKI ranged from 32% to 46%, and it has varied in different studies depending on the severity of the disease and the need for hospitalization and/or intensive care.

In a retrospective, observational study comprising a cohort of 3993 hospitalized patients diagnosed with COVID-19, AKI occurred in 1835 (46%) patients and 19% of those with AKI needed dialysis. Stage 3 AKI was present in 42% of cases. Of those hospitalized in the intensive care unit (ICU), 76% had AKI. Among the cohort of patients with AKI, proteinuria, hematuria, and leukocyturia were found in 84%, 81%, and 60%, respectively.

Patients with CKD, especially those on dialysis, those receiving immunosuppressive therapy, and KTRs, are at increased risk of getting infected with COVID-19, developing more severe disease, requiring hospitalization, and being at a greater risk of adverse outcomes including mortality. Analysis of the NHS Digital Trusted Research Environment for England (NHSD TRE) database from March 2020 to March 2021 showed that after adjusting for age, gender, COVID-19 vaccinations, and positive COVID-19 test results with adequate matching, patients on dialysis or transplantation had the highest relative risk of 1-year all-cause death associated with SARS-CoV-2 infection (prevalent CKD: relative risk, 1.70; 95% confidence interval [CI], 1.67–1.73). This vulnerability is attributed to the attenuated activation of innate and adaptive immune systems in patients with CKD. Patients with CKD, especially those on dialysis, also show delayed viral clearance. ^,

The COVID-19 pandemic has had many repercussions on the delivery of care to patients with kidney disease. These effects included interruptions in dialysis delivery, delayed kidney biopsies, prolonged waiting times for arteriovenous fistula surgery and salvage procedures, disruption of kidney transplant services, interruptions in the supply chain of lifesaving drugs and disposables, and psychological distress to patients, family members, and caregivers including health care professionals. Studies have also suggested a significant association between the COVID-19 epidemic and high perceived stress among KTRs.

Nephrotic or nephrotic-nephritic presentations due to a range of glomerular diseases (see later) have been reported in COVID-19. Further, relapses of nephrotic syndrome in children and recurrences of antiglomerular basement disease have also been documented. ^, In addition, a second or third dose of the COVID-19 vaccine was associated with a higher relative but a low absolute increased risk of relapse in patients with glomerular disease.

The development of kidney injury in COVID-19 involves multiple mechanisms including direct cytotoxicity, hypercoagulation, virus-induced cytokine storms, activation of the angiotensin II pathway, complement dysregulation, and microangiopathy.

The virus can enter kidney cells through the interaction between the receptor-binding domain (RBD) of the spike protein of the virus and the angiotensin-converting enzyme II (ACE2) present on the surface of proximal tubular cells and podocytes. Subsequently, the spike protein undergoes proteolytic cleavage mediated by the transmembrane protease serine 2 (TMPRSS2). Podocytes and proximal tubular cells expressing the ACE2 gene have been identified as key host cells for SARS-CoV-2. SARS-CoV-2 can also infiltrate host cells via CD147, a transmembrane glycoprotein widely expressed on proximal tubular cells. ^, After entering cells, SARS-CoV-2 releases its constituents, replicates, and infects other cells. Kidney macrophages interact with viruses and stimulate phagocyte and chemokine signaling. The cytopathic impact of the SARS-CoV-2 virus can directly harm renal tubular cells during infection and replication, triggering an intricate immunologic response. Activated lymphocytes in the renal interstitium initiate renal cell destruction, leading to the release of proinflammatory cytokines such as perforin and granulysin. The resulting cytokine storm may contribute to AKI. Interleukin-6, a key cytokine, induces the secretion of other proinflammatory chemokines and cytokines and increases kidney endothelial vascular permeability, contributing to microcirculatory dysfunction. Natural killer cells and CD4 ⁺ T cells infiltrate the tubular interstitium and secrete proinflammatory cytokines, causing tubular damage, fibrosis, and apoptosis. Activation of the coagulation pathway contributes to microvascular thrombosis. In addition to factors related to the infection, AKI in critically ill patients with COVID-19 can be attributed to nonspecific factors including mechanical ventilation, hypoxia, hemodynamic instability, cardiac dysfunction, and the use of nephrotoxic agents. Fig. 59.2 shows the pathogenesis of renal dysfunction in patients with COVID-19.

Pathogenesis of kidney injury in patients with coronavirus 2019.

ECMO , Extracorporeal membrane oxygenation; MAC, membrane attack complex.

Several studies investigating native kidney biopsy and autopsy specimens have consistently shown acute tubular necrosis (ATN) to be the predominant pathologic finding in individuals with AKI with COVID-19.

Numerous glomerular diseases have also been documented in association with SARS-CoV-2 infection. The establishment of a definitive link between the development of glomerular disease and SARS-CoV-2 infection presents challenges because the role of this virus as either a primary cause or a contributing secondary hit in persons with a preexisting predisposition to glomerular pathology remains ambiguous. Several reports have documented the development of collapsing glomerulopathy, characterized by acute podocytopathy in the context of COVID-19, and the condition has been designated as COVID-19–associated nephropathy (COVAN). Endothelial tubule-reticular inclusions are a characteristic sign of COVAN and are linked to high circulating levels of interferon. The high-risk APOL1 genotype represents the main risk factor for the development of COVAN. In addition, there have been reports of the development of new-onset podocytopathy (focal segmental glomerular sclerosis and minimal change diseases [MCD]) and vasculitis (pauciimmune crescentic GN and antiglomerular basement diseases) in association with COVID-19. ^{, ,} Cases of membranous nephropathy (MGN) have been reported, with the suggestion that the presence of phospholipase A2 receptor (PLA2R) in the respiratory tract may serve as a possible site for antigen presentation, inciting or enhancing anti-PLA2R responses. Thrombotic microangiopathy (TMA) has also been reported in COVID-19, either as the predominant manifestation or alongside other findings such as ATN and collapsing glomerulopathy. ^, SARS-CoV-2 has been isolated from urine samples of patients with COVID-19. Evidence for the presence of SARS-CoV-2 has been found in all kidney compartments examined using reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization (ISH), and indirect immunofluorescence (IF) with confocal microscopy. ^,

Autopsies of kidney tissues obtained from patients with COVID-19 have revealed ATN and glomerulosclerosis. ^{, ,} Staining for S1 protein was found in renal parenchymal and tubular epithelial cells. Positive staining of NSP8, necessary for viral RNA synthesis and replication, suggests active viral replication in the kidney. The detection of viral proteins by electron microscopy (EM) provides confirmatory evidence of SARS-CoV-2 infection in kidney tissue. ^, Single-cell RNA sequencing has revealed evidence of injury and activation of profibrotic signaling pathways in human-induced pluripotent stem cell–derived kidney organoids infected with SARS-CoV-2. Infection with SARS-CoV-2 also resulted in elevated expression of the collagen 1 protein in organoids, suggesting that SARS-CoV-2 can directly invade renal cells, leading to cellular damage and fibrosis.

AKI has been associated with an increased mortality in individuals hospitalized with COVID-19. In a study of 3993 COVID-19 patients hospitalized with COVID-19, the in-hospital mortality rate was 50% among individuals who had AKI, compared with 8% among those who did not develop AKI. Furthermore, the kidney function did not return to baseline in 35% of the AKI survivors. In the STOP-COVID Cohort Study, which included 4221 ICU patients, more severe AKI was associated with increased mortality. Sixty-seven percent of the 876 patients who needed kidney replacement therapy (KRT) died, 11% had nonrecovery of kidney function, and 22% showed full kidney recovery at the time of discharge. In a cohort analysis of patients with in-hospital AKI (182 COVID-19–associated AKI and 1430 non–COVID-19 AKI), COVID-19–related AKI was associated with a greater rate of estimated glomerular filtration rate (eGFR) decline after discharge, regardless of underlying comorbidities or AKI severity. The fully adjusted model controlling for comorbidities, peak creatinine level, and in-hospital dialysis requirement showed a greater reduction in eGFR in COVID-19–associated AKI (–14.0; 95% CI,–25.1 to–2.9 mL/min/1.73 m ² /year; P = 0.01). This eGFR trajectory emphasizes the need for long-term monitoring of renal function in patients with COVID-19–associated AKI.

After controlling for demographics and comorbidities, population-based studies show a higher mortality rate in dialysis patients with COVID-19. ^, The age-matched relative risk of death from COVID-19 for an in-center hemodialysis patient compared with the general population ranged from 432 for a 20- to 39-year-old patient to around 10 for a patient aged >80 years.

The COVID-19 pandemic intensified the challenges associated with organ transplantation. Transplant centers globally experienced a decrease in the number of kidney donations from both deceased and living donors. KTRs with COVID-19 had increased fatality rates, likely attributable to compromised immune responses resulting from prolonged administration of immunosuppressive medications, as well as the high prevalence of comorbid conditions such as diabetes and cardiovascular diseases. ^, A retrospective analysis of graft-related outcomes in the United Kingdom revealed that transplantations performed before and during the COVID-19 pandemic exhibited similar rates of primary nonfunction, delayed graft function, acute rejection, reoperation, length of hospital stay, and graft survival. A study comparing 56 patients waitlisted for a kidney transplant and 80 KTRs diagnosed with COVID-19 showed that despite similar demographic profile and comorbidity burden, waitlisted patients had higher rates of hospitalization and an elevated mortality risk. Whether immunosuppression should be reduced in KTRs with COVID-19 is not clear. While immunosuppression reduction has been a common practice, some studies have found that reducing immunosuppression may increase the risk of graft rejection. ^, Therefore the decision to reduce immunosuppression, typically involving antimetabolites or calcineurin inhibitors, should be individualized, considering the balance between disease severity and risk of rejection. ^{, ,}

Management of COVID-19 is primarily dictated by patient age, underlying health conditions, and disease severity. In addition to supportive measures, the range of therapeutic approaches includes antiinflammatory agents, anticoagulants, monoclonal antibodies, and antiviral therapies, individually or in combination. Despite being an important risk factor for severe and fatal COVID-19, clinical trials of drugs for COVID-19 have systematically excluded individuals with impaired kidney function. As a result, the appropriate dosage, frequency, and safety of these pharmaceuticals for individuals with CKD are not clear.

Several guidelines have been developed for the pharmacotherapy of COVID-19. All recommend the use of dexamethasone for severe COVID-19. The antiviral remdesivir, an RNA-dependent RNA polymerase inhibitor, is recommended for hospitalized individuals. Sulfobutylether-β-cyclodextrin, which serves as a carrier for intravenous administration of remdesivir, has the potential to accumulate within the renal tubules and cause nephrotoxicity. Remdesivir has, however, been used safely in COVID-19 patients with AKI and CKD. A study on hospitalized COVID-19 patients with eGFR from 15 to 60 mL/min/1.73 m ² found no statistically significant differences in peak creatinine levels during hospitalization, creatinine doubling, or KRT initiation between remdesivir-treated patients and matched untreated historical comparators. The U.S. Food and Drug Administration has approved remdesivir for treating COVID-19 in patients with advanced kidney disease including those on dialysis.

The combination of remdesivir and baricitinib, a Janus kinase inhibitor, reduces the recovery time in patients with COVID-19. This effect is particularly significant for individuals receiving high-flow oxygen or noninvasive ventilation. The use of nirmatrelvir-ritonavir was associated with a decrease in all-cause hospitalization and all-cause mortality in patients with CKD and COVID-19. ^, Vilobelimab, an anti-C5a monoclonal antibody that specifically targets an inflammatory pathway, also received Food and Drug Administration authorization for use in hospitalized COVID-19 patients who have initiated invasive mechanical ventilation or extracorporeal membrane oxygenation within a 48-hour duration.

Various vaccines for COVID-19 have been developed, such as the mRNA vaccines BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna), the viral vector vaccine ChAdOx-1 nCoV-19 (University of Oxford/AstraZeneca), the recombinant spike protein (S-protein) subunit vaccine NVX-CoV2373 (Novavax), and the inactivated whole-virus SARS-CoV-2 vaccine. Given the increased risk of acquiring the SARS-CoV-2 infection and the case fatality rate from COVID-19, patients with CKD, especially those on dialysis, have been prioritized for vaccination in many countries.

In general, the seroconversion rate following the COVID-19 vaccine in dialysis patients is lower than that in the general population. ^, The Dutch REnal Patients COVID-19 VACcination (RECOVAC) Consortium evaluated the immunogenicity of the mRNA-1273 COVID-19 vaccine in CKD stages G4–5, KTRs, and controls. Transplant recipients had a lower rate of seroconversion compared with the control group (56.9% vs. 100%, P <0.001). The study showed a high seroconversion rate among those with CKD G4-5 (100%) and those undergoing dialysis (99.4%). However, the average antibody concentrations in both the CKD G4-5 cohort and dialysis cohort were comparatively lower than those in the control group. In contrast, some studies have shown reduced seroresponse rates in patients undergoing dialysis after receiving two doses of the COVID-19 vaccine, as compared with healthy controls (≈80%). ^, Furthermore, the findings of the Dia-Vacc study indicate that over time, both dialysis patients and KTRs are at risk of a decline in IgG and receptor-binding domain-IgG (RBD-IgG) antibodies. Six months after vaccination, 98% of the control group continued to show antibodies, whereas the rate had dropped in the dialysis patients and KTR groups to 91% and 87%, respectively ( P = 0.005). The peak antibody titers are lower in KTRs, with an accelerated drop thereafter.

Suboptimal immunogenicity, waning antibody levels, breakthrough cases in fully vaccinated individuals, and ambiguous efficacy against COVID-19 have prompted the implementation of supplementary booster doses of the COVID-19 vaccine for patients undergoing dialysis and KTRs. ^, Housset and colleagues evaluated the effects of a fourth dose of mRNA vaccination administered after a median duration of 7.6 months following the third dose in dialysis patients. They showed a significant antibody response and raised antispike antibody titers. There is no discernible disparity in the safety profile of COVID-19 vaccination between individuals undergoing dialysis and the general population.

In CKD and dialysis patients, the incidence of mortality risk is significantly lower in those who are vaccinated than nonvaccinated. ^{, ,} In a retrospective analysis including adult patients undergoing chronic dialysis, after adjusting for age, sex, and Charleston comorbidity index, vaccinated patients had a significantly decreased composite risk of mortality or hospitalization (odds ratio 0.24, 95% CI 0.15–0.40).

The effectiveness of the COVID-19 vaccination in KTRs is suboptimal. A meta-analysis showed that KTRs had a lower seropositivity rate (26.1%) after two COVID-19 vaccination doses than patients on hemodialysis (84.3%) or peritoneal dialysis (92.4%). Vaccines had similar side effects in KTRs as in phase III studies of the general population. No instances of the development of donor-specific antibodies following vaccination were reported.

There have been reported instances of new-onset and relapsed kidney diseases following the administration of COVID-19 vaccines. The nephropathies reported post COVID-19 vaccination include MCD, immunoglobulin A nephropathy (IgAN), MGN, antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis, acute interstitial nephritis (AIN), and TMA. The reported incidence of cases is small compared with the vast number of vaccine doses administered, and the advantages of COVID-19 immunization significantly outweigh any possible risks.

Annually, around 400 million cases of dengue are reported globally, resulting in roughly 22,000 fatalities. The disease is endemic in more than 100 countries including regions of Africa, the Americas, the Eastern Mediterranean, Southeast Asia, and the Western Pacific. According to the World Health Organization (WHO), the incidence of dengue has increased from approximately 505,000 in 2000 to 5.2 million in 2019. Disease transmission is affected by the ambient temperature and the virus genotype. Ongoing global warming is creating an environment hospitable to the spread of both the Aedes mosquito and the virus, leading to the spread of the disease in the subtropical parts of the world, such as Europe, where it did not exist until recently. The number of imported dengue cases in France went up from 217 in 2022 to 1414 in 2023, and new-onset local transmission of the disease has been documented in Italy, Spain, and France.

Disease presentation ranges from mild fever to severe, life-threatening multiorgan involvement. In 1977 the WHO classified dengue infection into asymptomatic infection, dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). In 2009, this classification scheme was revised to dengue without warning signs, dengue with warning signs, and severe dengue. Patients with kidney failure on dialysis are at risk of developing severe disease.

The ratio of asymptomatic to apparent infections is about 15:1. The disease has three phases: febrile, critical, and recovery. The main features include fever, myalgia, headache, arthralgia, retroorbital pain, body rash, lymphadenopathy, and hematologic anomalies including thrombocytopenia, increased hematocrit, and leukopenia. DHF is distinguished by the presence of increased vascular permeability and profound vascular leakage. DSS is a severe complication characterized by hypovolemia and compromised peripheral perfusion, leading to tissue damage and multiorgan failure. Individuals are at higher risk for severe dengue infection when they experience sequential dengue infections with two different strains of dengue virus.

Kidney manifestations of DF include proteinuria, nephrotic syndrome, and AKI. Cases of hemolytic uremic syndrome (HUS) characterized by AKI and clinical and histologic signs of TMA have been reported in DF. The prevalence of dengue-associated AKI varies across studies, with reported rates ranging from 0.9% to 70%. In a large retrospective cohort involving 1484 individuals, 4.8% of patients had AKI, and 14.1% of those with AKI underwent dialysis.

The diagnosis of dengue can be made by detecting viral genetic material by RT-PCR or viral antigen nonstructural protein 1 (NS1). In primary infections, the sensitivity of NS1 detection exceeds 90%. The diagnosis can also be confirmed by demonstrating a rising antibody titer (IgM and/or IgG).

Dengue virus can directly or indirectly damage the kidney through shock, renal hypoperfusion, or immunologic dysfunction. Other possible mechanisms include hemolysis and rhabdomyolysis. DHF/DSS represents the development of an aberrant and exacerbated immune response by the host. Initial activation of CD4 ⁺ cells initiates both Th1-mediated and Th2-mediated responses, leading to the release of multiple cytokines, namely interleukin-2 (IL-2), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α), which can cause tissue injury. Viral antigens have been documented in glomerular and tubular tissues, suggesting direct tissue damage. ^,

Renal histopathology in dengue patients has shown a range of lesions including proliferative GN, membranoproliferative glomerulonephritis (MPGN), TMA, ATN, pigment nephropathy, and IgA mesangial deposits. ^, IF shows the presence of glomerular IgG and/or IgM and C3 deposits, suggesting immune-mediated injury. Microtubuloreticular structures have been identified on EM, indicating a possible viral infection.

Treatment of DF is largely supportive. In the early stages of the disease, care involves monitoring vital parameters such as blood pressure, hematocrit levels, platelet count, urine output, and consciousness. Prompt restoration of the circulation volume by using crystalloid solutions is crucial. Platelet transfusions may be warranted in patients with severe thrombocytopenia (<10,000/mm ³ ) and active bleeding.

AKI should be managed in the usual way with supportive treatment including KRT as needed. Recovery from uncomplicated dengue usually takes 2 weeks. In one study, the mortality rate among patients with AKI was 12.7%, whereas in other studies, the case fatality rate among individuals diagnosed with DF and AKI was around 60%. ^{, ,} Malhi and colleagues showed that among survivors of patients with dengue-associated AKI, 23% showed persistently low eGFR (<60 mL/min/1.73 m ² ) 3 months after discharge.

Two dengue virus vaccines (Dengvaxia and Qdenga) have been shown to protect people with laboratory-confirmed prior dengue virus infection from dengue infection by 60% to 80% and to prevent severe dengue that leads to hospitalization by 70% to 90%. These vaccines have been recommended by the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices and WHO. The Dengvaxia vaccine is approved for use in individuals aged 9 through 45 years, whereas the WHO recommends Qdenga for children aged 6 to 16 years in high dengue-burdened areas. These vaccines, however, raise the risk of severe dengue infection in dengue-naïve children and hence are not recommended. In a recent randomized controlled trial, administration of the Butantan-Dengue vaccine was effective in preventing symptomatic infections of DENV-1 and DENV-2, irrespective of dengue serostatus, over a 2-year follow-up period. A systematic review also showed that dengue vaccines could confer protection against severe dengue in pediatric populations.

An innovative biocontrol strategy for dengue control is infecting the A. aegypti mosquitoes with the gram-negative bacterium Wolbachia. Upon release in endemic areas, Wolbachia -infected mosquitoes mate with uninfected mosquitoes, reducing their reproductive capabilities, lifespan, and vector competence through several mechanisms. This approach might allow vector control without posing risks to natural ecosystems or requiring genetic modification of the mosquitoes.

The global prevalence of M. tuberculosis (Mtb) infection is estimated at approximately 2 billion. However, only a minority of infected people develop TB. Annually, the number of people becoming ill with TB is estimated at 10 million, with 1.3 million deaths. Most of these individuals reside in low- and middle-income countries, with approximately 50% in Bangladesh, China, India, Indonesia, Nigeria, Pakistan, the Philippines, and South Africa. Tuberculosis is the main contributor to infectious disease mortality on a global scale.

Risk factors for the development of TB include malnutrition, human immunodeficiency virus (HIV) infection, diabetes mellitus, chronic kidney and liver disease, homelessness, poor housing conditions, and the use of immunosuppressive medicines. Patients with kidney failure including those on dialysis and KTRs have a 10- to 50-fold greater TB rate than the general population. The primary mode of disease transmission is interpersonal, through inhalation of droplet aerosols containing bacilli. Additional mechanisms are prenatal transmission, accidental inoculation, sexual transmission, and therapeutic instillation.

After primary infection, Mtb bacilli undergo local multiplication in tissues and trigger a diverse range of immunologic responses. These reactions can lead to either eradication of the bacteria or their containment through the formation of granulomas, also known as the “primary Ghon focus.” Primary TB lesions are commonly observed in the lungs, tonsils, or gastrointestinal tract, although all organs can potentially serve as a site of infection. The bacilli travel through the lymphatics to the nearby lymph nodes. The infection remains contained because of slow multiplication, intracellular localization inside macrophages, and development of acquired immune responses. Any immunosuppressed status, such as CKD, that diminishes the activity of cell-mediated immune reactions facilitates the multiplication of tubercle bacilli. This persistent and dynamic interaction between the organism and host immune response determines the development of sequelae-like caseous necrosis, abscess, ulceration, fistulae, fibrosis, or calcification if the host’s immune system is unsuccessful in eliminating MTB.

Urogenital tuberculosis (UG-TB) encompasses the involvement of several organs within the genitourinary system including the kidneys, ureters, bladder, prostate, urethra, penis, scrotum, testicles, epididymis, vas deferens, ovaries, fallopian tubes, uterus, cervix, and vulva. Two studies from the United Kingdom reported the frequency of UG-TB to be 27% in 1989 and 1.8% in 2019. In addition to the natural reduction in prevalence, varying notification practices could have accounted for this difference. Only a small percentage of people diagnosed with kidney TB have concurrent pulmonary TB, with approximately 10% of cases presenting with active pulmonary TB. About one-third of patients exhibit an abnormal chest radiograph. ^, In India, genitourinary TB comprises 20% of all extrapulmonary TB and is the most common extrapulmonary system to be affected by this disease.

For reasons that are not clear, UG-TB is encountered twice as frequently in men as women. The disease is seen more frequently among ethnic minorities in developed countries. In Western countries, UG-TB presents in the fifth to seventh decades, whereas no age predilection is noted in developing countries. There are no specific presenting features, often causing the disease to be overlooked until the late stages. One of the classical presentations is sterile pyuria in someone with dysuria and/or frequency. The typical symptoms of TB, such as fever, night sweats, nocturia, and weight loss, are not common but strengthen clinical suspicion when present. Rare symptoms include back, flank, or abdominal pain and macroscopic hematuria. Genital involvement can present with epididymo-orchitis or prostatitis, manifesting with pelvic discomfort, dysuria, hematospermia, sexual dysfunction, hesitancy, and difficulty in urination. There have been case reports of patients presenting with AKI and found to have granulomatous interstitial nephritis on kidney biopsy. Resolution of AKI following antitubercular therapy strengthens the etiologic association.

UG-TB may go overlooked due to its nonspecific symptoms, long-lasting and ambiguous clinical presentations, and a lack of knowledge among health care professionals. Diagnosis requires a high index of suspicion, with confirmation by a bacteriologic examination or tissue biopsy. Demonstration of TB bacilli in the urine requires repeated (three to six times) testing on successive days of early-morning urine samples for acid-fast bacilli (AFB) by Ziehl Nielsen staining, mycobacterial culture, or PCR. The AFB smear microscopy technique requires a minimum concentration of 5 × 10 ³ bacilli per milliliter of the specimen. ^, Light-emitting diode-based fluorescence microscopy has replaced traditional Ziehl Nielsen staining because it provides a faster diagnosis. Further, the demonstration of AFB is not always diagnostic since the urinary tract may be colonized by environmental mycobacteria, especially in swimmers. The culture of clinical specimens for Mtb is widely regarded as the most reliable diagnostic approach for identifying active TB, with a specificity of 100% and a sensitivity of 65%. ^{, ,} Historically, the conventional approach involved employing the solid Lowenstein-Jensen culture medium, which necessitated a time frame of 6 to 8 weeks. This method has been substituted by the automated liquid mycobacteria growth indicator tube (MGIT) culture, which employs the BACTEC MGIT 960 System (Becton Dickinson, Franklin Lakes, New Jersey, USA) and can confirm the growth of microorganisms in approximately 2 weeks. The GeneXpert MTB/RIF assay is a cost-effective and expeditious diagnostic tool. It enables the simultaneous detection of Mtb and rifampicin resistance. GeneXpert demonstrates a superior performance compared with AFB smear and culture in detecting M tuberculosis in urine samples. The TB-LAM (lipoarabinomannan) urine test is recommended for the diagnosis of HIV-associated TB because patients with advanced immunosuppression are at an increased risk of disseminated Mtb infection, which results in renal involvement and the release of heat-stable Mtb LAM glycolipid into the urine.

Radiologic tests (intravenous urography, computed tomography scans, or ultrasound) that show concomitant upper and lower urinary tract involvement strongly support a diagnosis of UG-TB. Classical radiologic features include mucosal thickening, cavities, strictures, calcification, and many other manifestations ( Fig. 59.3 ). Imaging facilitates the precise guidance of procedures such as abscess aspiration or tissue biopsy, allowing for microbiologic and molecular evaluation. Those with negative bacteriologic, nucleic acid, or radiographic findings may need a tissue biopsy of the urinary tract or the kidney showing caseating granulomata with or without AFB. A rare manifestation is hypercalcemia due to the aberrant extrarenal synthesis of 1,25-dihydroxyvitamin D3 by activated macrophages within the granulomatous tissue.

TB radiology: radiologic abnormalities in genitourinary tuberculosis.

(A) An intravenous urogram showing infundibular stenosis, pelvic scarring, irregular dilatations of calyces, and cavitations of the right kidney. (B) Computed tomography (CT) urography showing destruction of parenchyma of left kidney (autonephrectomy), with thickened pelvicalyceal system and ureter. Right kidney is obstructed due to poorly compliant, fibrosed, and thickened bladder wall with reduced capacity. (C) Plain CT scan showing lobar calcifications in the left kidney.

Image courtesy Dr. Anupam Lal and Dr. Shrawan K. Singh.

Tubercle bacilli can colonize the kidneys through hematogenous or lymphatic spread after the original infection from the lungs or gut. The initial seeding is usually within the cortex, near the glomeruli or the peritubular capillary bed. When the bacilli pass into the nephrons, they become entrapped within the loop of Henle, producing new foci of infection. The resulting granulomatous inflammation and its progression contribute to the development of chronic tubulointerstitial nephritis, papillary necrosis, fibrosis, and extensive caseous destruction of the renal parenchyma. Multiple microscopic foci of necrosis can coalesce, giving rise to macroscopic lesions that involve the renal papilla. Destructive inflammation, cavities, and vascular insufficiency cause papillary necrosis. Tubercular pyelonephritis may progress to pyonephrosis with increasing fibrosis and scarring of the renal pelvis with dilation of the calyces. These processes unfold over the years.

Renal parenchymal involvement in TB ( Fig. 59.4 ) has been classified into four stages. Stage 1 is a nondestructive kidney parenchymal TB, which is evident only histologically. Minimal destruction associated with TB papillitis characterizes stage 2. More destruction leads to the formation of cavities (stage 3), and the final stage 4 is the extensive and highly destructive polycavernous kidney TB. Dystrophic parenchymal calcification is common and may be seen in stages 2 to 4. Unabated progression can lead to the development of “putty kidney” characterized by the presence of sacs containing caseous, necrotic material, and dystrophic calcification, often associated with autonephrectomy.

(A) Gross image of end-stage kidney disease secondary to multiple cavities in the calyces, filled with gray-white friable pultaceous material. The ureteric wall is thickened, forming megaureter; (B) Scanner and low magnification view of kidney tissue showing numerous granuloma with central necrosis, admixed with Langhan multinucleate giant cells (PAS stain); (C) Core biopsy of the kidney shows epithelioid cell granuloma with central breakdown and Langhan giant cells (PAS, 20×); (D) Acid-fast bacillus in renal tissue (Ziehl Nielsen stain, 100×).

Image courtesy Dr. Mahesha Vankalakunti.

TB can involve all compartments of the kidneys and urinary tract. The most common presentation is chronic tubulointerstitial nephritis with granulomas. Chronic TB may lead to the development of secondary amyloidosis. The relationship between TB and other types of GN remains inconclusive, with several case reports of focal proliferative GN with the presence of immune system deposits, MGN, mesangiocapillary glomerulonephritis, and crescentic GN.

Inflammation from renal TB can extend into the perirenal and pararenal regions including the psoas sheath, resulting in the formation of cold abscesses, sinus tracts, and fistulae. mTB bacilli from the kidney spread into the ureters to cause inflammation, edema, granulomatous ulceration, and fibrosis. These pathogenic processes cause irregular ureteric strictures, segmental dilatation, obstruction, and reflux. Chronic inflammation and ureteric strictures lead to hydroureteronephrosis. An alternating pattern of nonconfluent dilatations and strictures may resemble a corkscrew or string of beads. The ureter may become shortened and stiff, known as a “pipe-stem ureter,” lacking peristaltic movement.

Other features include cystitis and fibrosis, stenosis, or strictures at the ureterovesical junction (giving the orifice a golf-hole appearance) and hydroureteronephrosis. Chronic bladder wall and detrusor muscle inflammation can cause thimble bladders (small capacity with an elevated base) due to thickening of the bladder wall with trabeculation and calcification. Vesicovaginal, vesicocolic, or enterovesical fistulae and bladder perforation are rare consequences of bladder TB. The retrograde spread of TB from the prostate or testes to the bladder has also been described.

Bilateral disease can lead to gradual deterioration in kidney function, ultimately leading to kidney failure. In a retrospective analysis of 56 patients with UG-TB, 20% and 7% of patients developed CKD and ESKD, respectively. AKI and old age were independent risk factors for CKD.

Treatment of drug-sensitive tuberculosis involves a 2-month intensive phase of chemotherapy consisting of daily administration of first-line tuberculosis medications, rifampicin, isoniazid, pyrazinamide, and ethambutol along with pyridoxine to prevent isoniazid-induced neurotoxicity. This is followed by a 4- to 6-month continuation phase in which two drugs, rifampicin and isoniazid, are given. Drug-resistant TB requires 18 to 24 months of treatment with potentially toxic second- or third-line agents.

No dosage adjustment is needed for isoniazid and rifampicin in individuals with renal impairment. The dose of pyrazinamide and ethambutol is halved in patients with a glomerular filtration rate (GFR) below 10 mL/min/1.73 m ^2, including those undergoing dialysis. Drugs can be given in full doses on alternate days or daily at 50% of the prescribed dose. It is advisable to use caution while administering streptomycin and ethambutol to patients with CKD due to the potential risks of ototoxicity and ocular toxicity, respectively.

Surgical interventions may be needed in certain circumstances including drainage of the obstructed pelvicaliceal system or abscesses, nephrectomy for nonfunctioning kidneys, ureteric reconstruction procedures, and reconstructive surgery of the bladder to improve functional bladder capacity reduction. Definitive surgery is usually delayed until after the active disease has been treated with chemotherapy. Stenting or percutaneous nephrostomy may be indicated for patients with ureteral strictures, especially if hydronephrosis is also present. In a study of 77 patients, early ureteral stenting or percutaneous nephrostomy was associated with a lower nephrectomy rate (73 vs. 34 percent). Nephrectomy may be considered in cases of extensive unilateral disease. Urinary tract lesions may progress despite effective treatment, and new lesions may appear due to inflammation and/or fibrosis.

Leprosy is transmitted by prolonged, close contact with individuals with untreated leprosy, usually through respiratory droplets. The disease has a long incubation period of several years. It presents with predominant cutaneous (hypopigmented or erythematous skin lesions or skin thickening) or neurologic involvement (paresthesia, hypoesthesia, or thickened nerves). The diagnosis is made by demonstration of typical histologic findings on full-thickness biopsy of the involved skin and nerves or a PCR for identification of M. leprae deoxyribonucleic acid (DNA). The disease spectrum is also affected by the host immune response—with fewer lesions and bacilli when the response is robust (paucibacillary or tuberculoid disease) and a greater number of lesions and higher bacillary load on biopsy in the case of a weaker immune response (multibacillary or lepromatous disease).

A precise estimate of the frequency of renal involvement cannot be made, with the presentation ranging from asymptomatic tubular function abnormalities to varying degrees of proteinuria and, less commonly, kidney failure. In one study, abnormalities in urinary concentrating ability were found in 83% and 85% of patients with paucibacillary and multibacillary leprosy, respectively. In another retrospective analysis from Brazil evaluating 923 patients, 4.8% exhibited proteinuria, 6.8% had hematuria, 10.4% showed leukocyturia, and 3.9% showed elevated serum creatinine. Most individuals had multibacillary leprosy. Hematuria is more prevalent among patients with multibacillary lepromatous leprosy, particularly during episodes of lepra reaction (an inflammatory response due to immune system activation, affecting 30% to 50% of patients with leprosy). A reduced GFR is associated with reaction episodes, multibacillary infections, and advanced age. Nephrotic syndrome is seen in those with amyloidosis, more frequently in those with lepromatous disease. ^{, ,} Multidrug therapy (MDT) has reduced the frequency of kidney disease. In one recent study, 45.5% of patients exhibited elevated serum creatinine at diagnosis, which decreased to 18% and 9% after 3 and 8 months of MDT. AIN secondary to dapsone or rifampicin has been reported rarely. ^,

The precise mechanism underlying kidney injury in leprosy remains incompletely elucidated, with immune complex–mediated injury resulting from the interactions between antigens originating from M. leprae and elevated levels of humoral antibodies targeting these antigens being the primary hypothesis. Abnormal cell–mediated immunity has also been demonstrated. Serologic investigations have indicated a decrease in complement hemolytic (CH50) activity and diminished levels of C4 in individuals with lepromatous leprosy, suggesting the activation of the classical or lectin pathway.

A wide range of histopathologic lesions have been observed. In an autopsy study of 199 patients from Brazil, 72% displayed renal lesions. The lesions included ATN, AIN, MGN proliferative GN, crescentic GN, MPGN, and amyloidosis. Epithelioid granulomas and lepra bacilli were also encountered. IF investigations reveal granular deposits of IgG within the mesangium and along glomerular capillary loops with variable deposits of C3, IgA, IgM, and fibrin. ^, EM shows electron-dense deposits in the mesangial, subendothelial, and subepithelial areas. ^,

Treatment entails standard multidrug therapy with dapsone, rifampicin, and clofazimine for 6 to 12 months. No specific treatment is required for renal lesions. A short course of corticosteroids may be administered to those with AIN.

Kidney involvement in scrub typhus is multifactorial—attributable to systemic inflammatory response syndrome, endothelial dysfunction, volume depletion, disseminated intravascular coagulation (DIC), rhabdomyolysis, and direct O. tsutsugamushi infiltration into the renal parenchyma, as demonstrated by the presence of the organisms within the renal tubules. Contributory factors include the need for intensive care, thrombocytopenia, pneumonia, shock, and acute respiratory distress syndrome (ARDS).

Respiratory distress, encephalitis, AKI, myocarditis, septic shock, and multiple organ dysfunction syndrome (MODS) are the leading causes of death among patients with severe disease. ^,

Descriptions of renal pathology in scrub typhus are mostly in the form of case reports. ATN, AIN, MGN, and mesangial hypercellularity with mesangial IGA deposition have been reported in renal biopsies. ^{, , ,} An autopsy series described kidney histopathologic changes in 69 scrub typhus patients. About 30% had focal or diffuse GN. ATN was found in all cases, with hemoglobin casts in the distal nephron in 69%. Another dominant finding was the presence of varying degrees of interstitial nephritis. The infiltration was most likely to occur near the corticomedullary junction. After the testicles, the kidneys were the second most common site of vascular alterations, such as hyperplasia of the endothelial cells of the glomerulus, thrombophlebitis with interstitial mononuclear infiltrate, and arteriolar necrosis.

The classical Weil-Felix test, a nonspecific agglutination test that detects antirickettsial antibodies, has low sensitivity and has been replaced by newer methods. Serologic assays such as indirect fluorescent antibody (IFA)- and enzyme-linked immunosorbent assay (ELISA)-based methods are the mainstay of diagnosis. PCR exhibits a higher sensitivity, enabling its utility in the timely identification of diseases at an early stage. Biopsy of eschar or rash can show typical intense lymphohistiocytic vasculitis and thrombosis, along with focal areas of cutaneous necrosis. Culture can be laborious and time intensive due to the obligate intracellular nature of O. tsutsugamushi and is available only in specialized centers.

Azithromycin and doxycycline are widely used efficacious antimicrobial agents for the treatment of scrub typhus. Tetracycline and rifampicin have also demonstrated efficacy. Combination therapy with intravenous doxycycline and azithromycin shows superior therapeutic efficacy compared with the use of either drug as a monotherapy. In a trial comparing monotherapy with combination, complications requiring organ support including dialysis were fewer by day 7 in the combination therapy group, with more frequent resolution of hepatic and renal involvement.

The case fatality rates due to scrub typhus vary, with a median mortality rate of 6.0% and 1.4% in untreated and treated patients, respectively. The fatality rate can be as high as 25% in those with MODS. Patients with AKI are at higher risk of mortality. ^{, ,} Higher rates have also been reported in patients who have oliguria and those who undergo dialysis. There has been a noticeable decline in fatality rates associated with scrub typhus infection in recent years, from 12% to 16% to 1.79%. ^, This improvement could be linked to the increased awareness resulting in rapid diagnoses and prompt commencement of treatment. Persistent urinary abnormalities or reduced GFR can be seen in a minority of patients. ^,

Leptospirosis is seen worldwide, with the highest prevalence in South and Southeast Asia, Oceania, the Caribbean, sub-Saharan Africa, and Latin America. According to a systematic review, more than 1 million individuals are affected worldwide, and 60,000 die every year. Outbreaks tend to develop in regions characterized by endemicity where housing and sanitary infrastructure are inadequate, particularly in the aftermath of intense rainfall or flooding. Global warming is leading to the expansion of the geographic areas optimal for survival and the spread of leptospires. The reemergence of leptospirosis in Tanzanian farmers was documented in 2022, with 20 verified symptomatic cases and three fatalities. According to the European Climate and Health Observatory, the higher temperatures and rainfall due to climate change will likely increase disease risk and spread to Europe. Nonimmune travelers to endemic areas are especially vulnerable. In fact, the yearly incidence of travel-related leptospirosis in Southeast Asia is greater than that of endemic cases (1.78 vs. 0.06 cases per 100,000 population).

The clinical manifestations of leptospirosis range from an asymptomatic or mild disease to a severe life-threatening illness. The disease typically presents in two phases—an initial bacteremic phase and a later immune phase. Common clinical presentations include fever, rigors, myalgias, nausea, vomiting, diarrhea, arthralgias, and abdominal pain. Jaundice, hemorrhagic manifestations, and conjunctival hyperemia are the distinguishing features of Leptospira infection. Organ-specific complications include AKI, liver dysfunction, respiratory failure, uveitis, myocarditis, meningitis, and rhabdomyolysis. Weil disease is the name given to the most severe presentation of leptospirosis, characterized by jaundice, AKI, and bleeding diathesis.

Kidney involvement is nearly universal and ranges from asymptomatic urine abnormalities to severe AKI. Abnormal urinalysis (leukocyturia, hematuria, and bile and granular casts); tubular function abnormalities (glucosuria, bicarbonaturia, uricosuria); and dyselectrolytemia (hypokalemia and hypomagnesemia) are common. AKI develops in 10% to 60% of cases and can be oliguric or nonoliguric. Although more frequent with severe disease, AKI can be seen in those with mild anicteric disease as well. Arrhythmia, oliguria, jaundice, crackles, hyperbilirubinemia, raised direct bilirubin level, increased activated prothrombin time, and leukocytosis were recognized as independent risk factors for the development of AKI.

In recent years, the possibility of endemic leptospirosis leading to the development of CKD, especially in agricultural workers, has been proposed. A longitudinal study from Sri Lanka demonstrated that 9% of patients who had AKI due to leptospirosis developed stage 3 CKD after 1 year. A population-based study conducted in Taiwan with a median follow-up of 8 years indicates that individuals who experienced AKI following infection with leptospirosis were at an increased risk of developing CKD. The risk was directly proportional to the severity of AKI. The hazard ratio (HR) for developing new-onset CKD in AKI requiring KRT compared with those without AKI group and in those with AKI without KRT compared with the non-AKI group was 7.79 (CI 5.29−11.47, P < 0.001) and 6.29 (CI 4.86−8.15, P < 0.001), respectively, after adjustments for age, gender, and comorbid conditions.

Diagnosis is based on clinical suspicion and confirmed by serological tests (IgG and IgM antibodies) or PCR in biological fluids. The latter is most likely to be positive in the acute bacteremic phase, and the former in the immune phase. Confirmation by serologic testing requires the demonstration of rising titers on repeat testing. RT-PCR exhibits higher sensitivity and specificity compared with regular PCR. Other tests include antigen detection, blood smears, and Leptospira culture.

The clinical Thai-Lepto-on-admission probability (THAI-LEPTO) score was developed by the Thai-Lepto AKI study group for presumptive early diagnosis of leptospirosis in those presenting with a high pretest probability of the disease on the basis of clinical suspicion. The scoring system has seven variables with weighted scores: low hemoglobin (3), hypokalemia with hyponatremia (3), hypotension (3), jaundice (2), muscle pain (2), AKI (1.5), and neutrophilia (1). The test has positive and negative predictive values of 87% and 58%, respectively, with a cutoff at 4. Kidney injury molecule-1 (KIM-1) has been identified as a promising marker for early prediction/early diagnosis of leptospirosis-associated AKI, but further studies are warranted.

The most common histologic findings in leptospirosis are ATN and AIN. A biopsy series of patients with leptospirosis showed either mesangial proliferation or no remarkable change in the glomeruli. Tubular degeneration and interstitial edema with cellular infiltrates of mononuclear and few eosinophils were seen in the tubulointerstitial compartment. There was deposition of C3 in the arteriolar wall in IF studies. Leptospiral antigen deposition was detected in the interstitium and tubular cells. Vasculitis has been reported rarely.

Kidney involvement is linked to direct invasion of the organ by the spirochete leading to cytopathic or immunologically mediated changes. Tubular and electrolyte complications are mostly related to the decrease in the activity of sodium-hydrogen exchanger isoform 3 (NHE3) in the apical membrane of the proximal tubule and decrease in the Na ⁺ /K ⁺ -ATPase on the basolateral aspect.

Hyponatremia is caused by increased urinary sodium loss, cellular sodium efflux due to Na ⁺ /K ⁺ -ATPase abnormalities, high levels of antidiuretic hormone (ADH), or resetting of the osmoreceptor. Downregulation of the sodium-potassium-2-chloride co-transporter (NKCC2) located on the medullary thick ascending limb of the loop of Henle also contributes to urinary losses of sodium and potassium. Leptospira -induced tubular damage renders the intraluminal electric charge positive, leading to reduced magnesium and calcium reabsorption.

The primary antigen of the bacteria, LipL32, adheres to the extracellular matrix of the tubular cells, interacts with Toll-like receptor 2, and induces the migration of inflammatory cells into the renal interstitium. The Leptospira outer membrane protein (OMP) can also induce host cellular damage by activating the complement system.

Activation of innate immunity via host Toll-like receptor-dependent cascades leads to the activation of nuclear factor–κB (NF-κB), kinases, and cytokines. A massive release of inflammatory cytokines leads to the development of a “cytokine storm.” Other factors, such as hypovolemia, jaundice, and rhabdomyolysis, associated with the acute illness, also contribute to the development of AKI.

Evidence has accumulated around the potential of leptospiral infection in the kidneys to induce renal inflammation and subsequent kidney damage. In cases where the kidney fails to recover fully and the infection persists, there is a possibility of the development of renal fibrosis. In vitro cell culture and in vivo animal studies have shown that the involvement of TGF-β1/Smad-Dependent Pathway and Wnt/-catenin pathways are associated with leptospirosis-related kidney fibrosis. In immunohistochemical and quantitative real-time PCR experiments, Leptospira -infected C57BL/6J mice produced renal fibrosis with persistent carriage of L. interrogans . Chou and colleagues studied the transcriptome profiles of kidneys of mice with adenine-induced and chronically Leptospira -infected kidneys and found evidence of chronic inflammation, activated T-helper 17 immune responses, and a high-level expression of indoleamine 2,3-dioxygenase 1 protein, suggesting the risk of progressive kidney injury.

Treatment entails a combination of supportive care and antibiotics. The latter can shorten the duration of disease and hospitalization and reduce AKI risk but does not affect overall mortality. Mild disease should be treated with oral doxycycline or azithromycin, while severe disease requires intravenous doxycycline, ceftriaxone, or cefotaxime. An acute inflammatory response to the clearance of spirochetes, characterized by fever, rigors, and hypotension (Jarisch-Herxheimer reaction), may develop in about one-fifth of cases and can lead to worsening of preexisting AKI or new-onset AKI. Steroids and plasmapheresis have been proposed as adjunct therapies in such cases. In severe disease, supportive care with KRT, ventilatory support, and administration of blood products is often required.

Leptospiral AKI has a mortality rate of 10% to 22%, and severe AKI with multiple organ failure has a higher mortality rate. ^, A study by Andrade and colleagues showed that daily dialysis reduced mortality to 16.7% in patients with leptospirosis who were on mechanical ventilation, compared with 66.7% in those who were dialyzed on alternate days.

Leishmaniasis refers to a collection of parasitic disorders caused by an obligate intracellular protozoan belonging to the genus Leishmania, transmitted to humans through the bites of phlebotomine sandflies. Annually, there is an estimated occurrence of 700,000 to 1 million new cases of leishmaniasis. Although it has a worldwide distribution, Asia, Africa, the Americas, and the Mediterranean are endemic regions. Individuals residing in economically disadvantaged regions with inadequate nutrition, forced migration, substandard living conditions, and compromised immune function are at higher risk.

Pathogenesis

ATN in leishmaniasis may be owing to ischemia caused by the parasite leading to the obliteration of small vessels. Parasitic invasion can trigger an inflammatory response, causing necrotizing tubulitis. Autopsy studies have shown that Leishmania can invade all compartments of the kidney. The immune system also actively participates, with immune complex deposition, macrophages, T cells, cytokines, and immunoglobulins all playing important roles in the development of immune-mediated renal damage. ^, Glomerular diseases could develop from immune complex deposition due to polyclonal activation of B lymphocytes by the parasite. ^{, ,} Fig. 59.7 shows the kidney biopsy of a patient with filariasis.

(A) Photomicrograph showing larva of microfilaria in the peritubular capillary lumen in a patient with acute kidney injury (hematoxylin-eosin [H&E] stain, 100×). (B) Acute interstitial edema and inflammatory cell infiltrate rich in eosinophils, as an allergic manifestation of filariasis (H&E stain, 40×).

Image courtesy Dr. Mahesha Vankalakunti.

Filarial worms and their larvae are parasitic round nematodes encountered in the tropics and cause a group of diseases called filariasis. The infection is transmitted to humans by arthropods, usually mosquitoes. After being released into the bloodstream, the larvae migrate to different tissues of the human body and develop into adult worms. The tissue environment where the worms reside determines the nature of the clinical presentation. Lymphatic filariasis caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori is the most common form of filariasis and is seen in sub-Saharan Africa, Southeast Asia, South Asia, the Pacific Islands, Latin America, and the Caribbean. Subcutaneous filariasis, caused by Loa loa, Mansonella streptocerca, and Onchocerca volvulus is encountered in equatorial Africa and South America, whereas serous cavity filariasis caused by Mansonella perstans and Mansonella ozzardi is seen in Africa and Latin America.

Echinococcosis (hydatid disease), a disease affecting both humans and animals, is caused by various species of the tapeworm Echinococcus. The life cycle of this parasite involves dogs as definitive hosts and sheep, cattle, goats, and pigs as intermediate hosts. Humans can also act as intermediate hosts, harboring the metacestode (larval) stage of Echinococcus known as “hydatid cysts.” Of the four species that infect humans, the disease is caused most frequently by E Echinococcus granulosus, followed by E. multilocularis . The disease is endemic in central Asia, western China, South America, eastern Africa, and the Mediterranean countries. Prevalence rates are as high as 2% to 9% in endemic regions.

The main risk factors for contracting the disease include contact with canids and involvement in livestock raising. In cases of primary cystic echinococcosis (CE), hydatid cysts may develop in virtually any organ of the human body. The primary infection is asymptomatic, followed by a long latent phase lasting months to years. Approximately 80% of CE patients exhibit involvement of a single organ, typically manifesting as a solitary cyst localized in the liver or lungs. Renal echinococcosis (RE) is less frequent than hepatic and pulmonary disease, constituting approximately 4% of hydatid disease cases.

Clinical Presentation

RE is usually asymptomatic. Cysts are detected during ultrasound screenings for unrelated reasons. However, some patients may experience a range of symptoms, such as fever, dull flank pain, nausea, vomiting, or lumbar or abdominal masses that resemble tumors. In a series of 147 cases, the most common symptom reported was lumbar or lumboabdominal pain in 84% of patients. Hydatiduria, or the presence of hydatid cysts in the urine caused by cyst rupture, was observed in 28% of the cases. Other reported symptoms included fever (70%), lumbar mass (10%), and hematuria (8%). In rare cases, a bladder hydatid cyst may cause urinary retention, urinary frequency, and urgency. Patients may exhibit eosinophilia, pyuria, and hematuria. The most common areas in the kidney for cysts to be located are the polar regions, followed by the mediorenal region. There have been case reports of glomerular lesions with hydatid disease–related nephrotic syndrome, with the histology showing MCD, MGN, MPGN, and amyloidosis.

Diagnosis

Imaging modalities such as ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) play a crucial role in diagnosing hydatid cysts. Ultrasound is particularly effective in detecting key indicators of hydatid disease. The commonest finding is a smooth, round, anechoic cyst, similar to a benign cyst. Additional findings such as hydatid sand, daughter cysts, and floating membranes within the cyst aid in the diagnosis. Ultrasound is recommended for screening in endemic areas and forms the basis for the internationally recognized classification by the WHO expert group and Gharbi classification. ^, Contrast-enhanced CT scans offer a more precise and detailed view of the cyst membrane, aid in identifying daughter cysts, and allow the differentiation of hydatid cysts from kidney abscesses and tumors. Differentiating between complex, multivesicular renal hydatid and other conditions, such as hemorrhagic cysts, chronic abscesses, and malignancies, is essential. The hypovascular nature of papillary renal cell carcinoma makes it a particularly important differential. Fig. 59.8 shows gross image of the resected kidney with hydatid cyst.

Gross image of the resected kidney (partial nephrectomy) showing a hydatid cyst containing multiple “daughter” cysts.

Image courtesy Dr Abhishek Singh, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India.

Several serologic tests have been developed for diagnosis, with IgG ELISA being the most sensitive and specific. Antigen-specific confirmatory tests can supplement the serologic findings. Zmerli and colleagues showed positivity in 80% cases of RE with a combination of indirect hemagglutination and ELISA. PCR tests may play a role in the future. Percutaneous aspiration is used in those with negative serology to look for hydatid membranes, protoscolices, or hooklets but carries the risk of anaphylaxis.

Treatment

Small cysts (<5 mm) can be managed medically with albendazole and monitored by imaging. Alternative approaches include percutaneous aspiration with or without injection of a sclerosant, laparoscopy, and surgery. The latter is the preferred approach for complicated cysts or where many daughter cysts exist. Depending on the remaining viable tissue, surgeons may opt for pericystectomy or nephrectomy. ^, It is imperative to prevent leakage from the cyst during surgery or aspiration to avoid recurrence or serious anaphylactic reactions. ^, Adjuvant treatment with albendazole, mebendazole, or praziquantel is recommended to prevent recurrence. ^{, ,}

Fungi of the order Mucorales, found in soil, decaying matter, and air, are ubiquitous in the environment with minimal intrinsic pathogenicity. However, in immunocompromised individuals such as patients with diabetes, kidney disease, and recipients of solid organ transplants, they can cause devastating and often fatal infections. The range of predisposing factors is continuously expanding including recent additions like COVID-19 infection, trauma, burns, desferrioxamine therapy for iron/aluminum overload, and intravenous drug abuse (particularly in people living with HIV). ^, Renal involvement in mucormycosis is mostly observed in the disseminated form, while cases of isolated renal involvement have been sporadically documented. ^, Notably, renal involvement has also been reported in immunocompetent individuals. Most infections are caused by Rhizopus spp. with Rhizopus oryzae and Rhizopus microsporus being the most frequently reported organisms, followed by Apophysomyces elegans, Rhizomucor spp., Lichtheimia corymbifera, and others.

Pathophysiology

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