12.2.1.1 Aetiology and Risk Factors

Gram‐negative bacteria are common causative organisms of upper urinary tract infections because they are in lower urinary tract infections. Escherichia coli (E. coli) is responsible for the majority of pyelonephritis cases (80%), but other organisms such as Klebsiella pneumoniae, Proteus mirabilis, Streptococcus faecalis, and Pseudomonas should be considered when choosing antibiotic therapy. Factors affecting bacterial virulence are key to infections. See Chapter 20 for more details. Although pyelonephritis can affect any population or age group, there are certain groups of patients at higher risk (Table 12.3).

12.2.1.2 Clinical Presentation

Acute pyelonephritis is a clinical diagnosis. Classically, it presents with symptoms of systemic upset (i.e. pyrexia, nausea, vomiting, anorexia, and lethargy) and more specifically with unilateral loin pain, worse over the renal or costovertebral angle.

Patients might complain of lower urinary tract infection symptoms (L‐UTI): frequency, urgency, dysuria, and offensive smelling urine.

Care must be taken in the initial assessment of patients with sepsis (Table 12.4). Severe sepsis has a reported mortality of 20–42% [4].

12.2.1.3 Pathophysiology of Sepsis

Inflammation caused by chemical, mechanical, or infective stimuli occurs and precedes healing. This is usually localised to the area of the stimuli; however, activation of inflammatory cascades on a systematic level can give rise to systemic inflammatory response syndrome (SIRS). For example, this can be initiated by the out membrane of gram‐negative organisms, the lipopolysaccharide layer or their endotoxins, or in gram‐positive organisms, the lipoteichoic acid, or peptidoglycan.

These triggers activate receptors on immune cells (neutrophils, macrophages, lymphocytes, and plasma cells) leading to production of pro‐inflammatory cytokines, tumour necrosis factor α (TNF α), interleukins (IL‐2, ‐6, and ‐8) and activation of the kinin, complement, and fibrinolytic system cascades. The cytokines, TNF‐α, and IL lead to the production of prostaglandins, leukotrienes, platelet‐activating factor, and phospholipase A2; these cause endothelial damage, which in turn causes capillary leakage. In addition, the activated neutrophils release nitric oxide, which leads to vasodilation (Figure 12.1). The activation of the coagulation systems leads to microthrombi formation leading to dysfunctional tissue perfusion.

These effects result in widespread microvascular injury, tissue ischaemia, and clinical manifestation of hypotension.

12.2.1.4 Investigation

Initial investigations should include urine analysis with bedside urine dipsticks to check for the pH, white blood cells, nitrites, and red blood cells.

Perform urine microscopy and culture to identify causative organisms and provide antibiotic sensitivities.

Send blood for full blood count (FBC) and urea and electrolytes (UE) as well as inflammatory markers such as C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Blood cultures must be sent for all pyrexial patients before antibiotic use. For those patients who present with septic shock lactate levels must be obtained via arterial blood gas measurement.

X‐ray of the kidneys, ureter, and bladder (KUB) should be carried out to assess for obvious renal stone disease or gas around the kidney (the later finding could suggest emphysematous pyelonephritis [EPN]). Renal tract ultrasound must be performed to rule out renal collecting system obstruction, stone disease, or malformations which may alter further investigations and management. Computed tomography (CT) scans, however, are becoming the standard imaging modality in the acute setting and should be considered if symptoms are >72 hours to exclude abscesses (Figure 12.2) [5].

12.2.1.5 Management

Management is determined by how unwell the patient is. Patients who are clinically well can be deemed as mild to moderate but those who require hospital admission can be defined as severe. In hospital settings, sepsis should be treated along an agreed protocol, such as the Surviving Sepsis campaign bundles [2]. In most cases, if the infection is severe enough to require hospitalisation, then management should be as a multidisciplinary approach and must include local high‐dependency unit (HDU) and intensive‐therapy unit (ITU) teams.

Until antibiotic sensitivities can be established, initial management is with broad‐spectrum antibiotic therapy targeted at gram‐negative organisms. Local antibiotic resistance is an important factor in deciding on antibiotic cover for patients. In mild to moderate cases of acute pyelonephritis, oral antibiotics may suffice. However, intravenous antibiotics will be required for severe infections, and once the pyrexia has settled, the intravenous antibiotics can be switched to oral antibiotics. Fluoroquinolone such as ciprofloxacin can be used as a first‐line therapy because most organisms are sensitive to them; however, local antibiotic guidelines should dictate appropriate antibiotic use [5].

12.2.2.1 Aetiology and Risk Factors

Any condition that reduces host defences or leads to abnormal drainage of the renal collection system predisposes one to renal abscess formation (i.e. diabetes mellitus, nephrolithiasis, or ureteric obstruction) [6].

Before the widespread use of antibiotics, renal abscess were due to haematogenous spread of gram‐positive bacteria such as staphylococci. Today the most common organisms are gram‐negative uro‐pathogens such as E. coli, Klebsiella spp., and Proteus spp.

12.2.2.2 Clinical Presentation

Symptoms are similar to any upper tract urinary infection (i.e. pyrexia, loin pain, and malaise). Symptoms may be acute over days and weeks or become chronic over months, which eludes to the likelihood of abscess formation. Very rarely the abscess may be ‘pointing’ (Figure 12.3).

12.2.2.3 Investigation

CT is the gold standard diagnostic investigation, with a renogram to assess kidney functionality.

12.2.2.4 Management

Abscess >5 cm are commonly drained percutaneously or with open surgery. Small abscesses (≤3 cm) are treated with antibiotics and expectant management. Abscesses of 3–5 cm can be treated with either modalities (i.e. drainage or conservatively with reportedly similar results) [6–8].

12.2.3.1 Aetiology and Risk Factors

Risk factors to development of pyonephrosis are attributed to any factor that causes hydronephrosis (e.g. ureteric obstruction by stones or cancer) with subsequent development of infection (i.e. infected obstructed system).

12.2.3.2 Clinical Presentation

Patients present with pyrexia, renal or costovertebral angle tenderness, and are acutely unwell with systemic toxicity. History might be eluding to aetiology and usually symptoms present for a few days or weeks prior to the worsening sepsis.

12.2.3.3 Investigation

Assessment of a patient who is acutely unwell should follow that of acute pyelonephritis. CT scans are the gold standard and will establish the diagnosis and aetiology as well as aid determination of the extent of the disease. CTs can show the presence of air in the system, stone burden, and degree of hydronephrosis, oedema, and thickening of the urinary tract as well as perinephric fat stranding. Isotope scans can assess kidney functionality. If not available, then X‐ray of the KUB could demonstrate air in the collecting system and ultrasound can identify hydronephrosis and echogenic material with in the collecting system, as well as perinephric fat stranding.

12.2.3.4 Management

Initial management should include resuscitation and intravenous broad‐spectrum antibiotics. Urgent decompression of the effected renal collecting system is the priority. Until decompression of the system is achieved, the patient will continue to deteriorate, hence, the need for urgent decompression. This can be achieved by either percutaneous drainage with a nephrostomy insertion or ureteric drainage with a ureteric stent.

12.2.5.1 Aetiology and Risk Factors

The majority (85%) of patients presenting with EPN have diabetes mellitus with 34% caused by an obstructive uropathy. Other risk factors such include: obstructive uropathy, immunosuppression, alcoholism, drug abuse, and neurogenic bladder; anatomical abnormalities have also been associated [10–12].

EPN affects woman more than men 4 : 1 [12]. This is thought to be due to the increased risk of urinary tract infections (UTIs) in women [11, 13, 14].

E. coli is the most common organism followed by Klebsiella, Proteus, and Pseudomonas species; coagulase‐negative Staphylococcus and Group D Streptococcus have also been implicated [11, 12, 15, 16].

12.2.5.2 Clinical Presentation

EPN is a life‐threatening condition with a high mortality rate. Patients present with pyrexia (75%), renal angle pain and tenderness (70%), haematuria (30%), pyuria (78%), and are profoundly unwell and exhibit signs of severe sepsis with 25% presenting in septic shock [12]. Patients are sometimes treated as pyelonephritis until they fail to respond to management. Nearly 45% present with associated acute kidney injury (AKI). Rarely crepitus may be felt in the region of the renal angle.

12.2.5.3 Investigation

All patients who are acutely unwell must first be resuscitated before specific investigation can be carried out. Initial work up should include a full history and clinical examination. Particular attention should be noted to rule out a new diagnosis of diabetes mellitus or previously known history of the disease. Further investigations follow that of acute pyelonephritis (bloods and urine analysis).

Once the patient is stable, then prompt imaging of the renal collecting system must be undertaken. X‐ray can be used to identify gas pattern shadowing with in region of the renal collecting system, but this can be non‐specific and only accurate in diagnosing EPN in 53% of patients [12]. Ultrasound again can demonstrate gas in or around the renal collecting system and should be considered if no other imaging modalities are available, with an accuracy of about 68% [12].

A CT urogram is the gold standard with a 100% accuracy in diagnosing EPN (Figure 12.4). There are two CT‐based scoring systems (Table 12.5).

12.2.5.4 Management

Initial management should include resuscitation, intravenous broad‐spectrum antibiotics, and adequate control of blood sugar levels. As the majority of causative organisms are gram‐negative bacteria, antibiotic therapy should target these until specific cultures and sensitivities are available.

Historically, antibiotic therapy coupled with open nephrectomy or surgical drainage was the treatment of choice. However, advances in the last decade have established image‐guided, percutaneous drainage under local anaesthetic as the intervention of choice for EPN. Figure 12.5 depicts a flow diagram of EPN management.

Once the patient is stable, then a MAG‐3 or dimercaptosuccinic acid (DMSA) can be performed to establish renal functionality.

12.2.5.5 Prognosis

In the past, mortality rates were quoted to be as high as 50%; however, with percutaneous drainage, meticulous medical management, and close support with the intensive care unit, survival rates have increased, with current predicted mortality rates of about 18% [12]. Although, the cause of the majority of cases, the presence of diabetes mellitus or nephrolithiasis play no role in increasing mortality rates, but septic shock was the greatest predictor with >50% attributed mortality.

12.2.6.1 Pathophysiology, Aetiology, and Risk Factors

Infections and urinary obstruction lead to engorgement and destruction of the renal parenchyma leading to suppuration, haemorrhage, and necrosis. This leads to abscess formation with deposition of granulomatous tissue with granular histiocytes and ‘foamy’ lipid‐laden macrophages. There is also fibrohistiocytoma‐like or plasma cell granuloma‐like patterns, and possible myofibroblast metaplasia. The affected kidney or section of kidney becomes grossly enlarged.

XPN is more commonly diffused, affecting the entire kidney; however, focal cortical or even segmental forms can occur.

Table 12.6 lists risk factors that can predispose to XPN; however, invariably stones are the culprit. E. coli and Proteus are the more common organisms; however, any of the uro‐pathogens can lead to XPN.

12.2.6.2 Clinical Presentation

Patients present in a similar manner to those with pyonephrosis or acute pyelonephritis. Symptoms include flank or loin pain, pyrexia, haematuria, and systemic upset. On clinical examination, it may be possible to ballot a renal mass on the affected side.

12.2.6.3 Investigation

Urine and blood cultures may be positive for common uro‐pathogens. Blood test may show renal dysfunction, anaemia, or leucocytosis. Inflammatory markers such as CRP and ESR will be elevated.

US imaging of the renal tract may demonstrate a dilated collecting system and an enlarged kidney containing echogenic material. CT scanning may show renal stones within the renal mass. Due to indistinct radiological appearance, XPN is indistinguishable from renal cell carcinoma. However, occasionally the ‘Bear Paw’ sign can be picked up on the cross‐sectional appearance of the kidney. The renal pelvis is contracted, whereas the calyces are dilated, mimicking the toe pads of the bear paw. The role of magnetic resonance imaging (MRI) is not well established in the context of XPN, and so is not routinely used. Radioisotope imaging will demonstrate a poorly or nonfunctioning kidney.

Definitive diagnosis can only be made with tissue analysis. Microscopic examination shows yellow nodules of pus, necrosis, and haemorrhage within the calyces.

12.2.6.4 Management

Most patients will initially be treated with antibiotics until their acute infection has settled. After diagnostic imaging, patients will proceed to a nephrectomy to rule out malignancy after which, the confirmation the diagnosis of XPN is usually made. Intraoperatively, XPN can be technically challenging due to the severe inflammation, which results in obliteration of tissue planes as they become fused together and become difficult to dissect.

12.2.6.5 Complications and Prognosis

Within the literature, there have been cases noted of sinus and fistula formation because of chronic infection. These can be to adjacent organs or structures (i.e. psoas abscess or even cutaneous) but are considered extremely rare [17, 18].

12.3.1.1 Introduction

Tuberculosis (TB) commonly manifests as a respiratory infection. Extrapulmonary TB can affect any part of the body with the kidney being the most common. Table 12.7 shows other genitourinary manifestation of TB.

12.3.1.2 Aetiology and Risk Factors

Tubercle bacilli reach the urinary tract via the bloodstream from a primary focus in the lung or bowel. There can also be tertiary spread from bone lesions. The bloodstream brings the mycobacteria to the kidney where they form multiple minute abscesses in the parenchyma (Figure 12.6), which later invade the tubule, erode into a calix, spread to other calices and the pelvis, and finally progress down the ureter into the bladder. Caseating granulomas are formed, which are Langhans giant cells surrounded by lymphocytes and fibroblasts. With the chronic infection, there is healing by fibrosis and calcification. The fibrous tissue contracts, leading to obstruction of one or more calices. The fibrosis eventually leads to destruction of the renal tissue, resulting in atrophic kidneys, ultimately leading to loss of functionality and autonephrectomy. Ureteric involvement leads to stricture formation at the vesicoureteric junction (VUJ) more commonly, followed by pelviureteric junction (PUJ) and mid‐ureter [19–22] (Figure 12.7). Involvement of the ureteric orifice leads to distortion, the ‘golf‐hole’ appearance, and may give rise to reflux.

The earliest lesions cannot be detected in the kidney until a small tuberculous abscess ruptures into the calix, giving rise to irritating symptoms and pyuria. Untreated, these abscesses enlarge, coalesce, and calcify until the entire kidney may be converted into a calcified mass, previously known as a ‘cement kidney’.

As the mycobacteria spread down the ureter, they cause patches of granuloma in its wall, and on reaching the bladder, similar granulomas form in the vicinity of the ureteric orifice. Sometimes these are so oedematous that they resemble a papillary tumour. Later in the disease, there is ulceration which may become confluent throughout the bladder.

12.3.1.3 Clinical Presentation

Initial symptoms include fever, night sweats, weight loss, lethargy, and failure of treatment for a persistent UTI. Late symptoms can include haematuria and loin pain. Patients may present with lower urinary tract infections that mimic cystitis or prostatitis.

A detailed history should be sought to illustrate previous TB infections or contact with persons infected with TB. A detailed travel history of the patient and their most recent contacts is also important.

12.3.1.4 Investigation

Examination may be unremarkable for these patients. Urine testing usually shows sterile pyuria and negative cultures. If TB is suspected, then three early morning urine samples (EMUs) should be sent for Ziehl‐Neelsen staining to confirm the presence of acid‐fast bacilli. Three samples are needed because the TB bacterium is excreted only intermittently in the urine; hence, multiple samples of urine that have been in the bladder overnight allow for a greater chance of detection. The specimen is cultured on Lowenstein‐Jensen medium; however, cultures can take up to four weeks because the TB bacterium’s doubling time is exceedingly slow (15–20 hours). Therefore, polymerase chain reaction (PCR) testing can also be carried out.

CT urogram and intravenous pyelogram (IVP) could show moth‐eaten calyces, renal calcification, cavitation of the renal parenchyma, hydronephrosis or hydroureter due to stricture, infundibular stenosis, and small shrunken kidney (autonephrectomy) [23] (Figures 12.8 and 12.9). Pelvic calcification may be seen due to vas, seminal vesicle or prostatic involvement.

Cystoscopy, retrograde studies, ureterorenoscopy, and biopsy can also be performed to assist in the diagnosis. Renograms can establish kidney functionality.

12.3.1.5 Management

Before the advent of effective anti‐tuberculosis drugs, nephrectomy and cavernotomy was the treatment of choice in such patients. Today, prompt diagnosis and initiation of appropriate antibiotic therapy is the cornerstone of management.

Six months of multidrug anti‐TB regimens are effective for urinary TB infections [24, 25]. Aggressive antibiotic use is to allow achievement of prompt eradication, decrease therapy duration as with individual medication, and the likelihood of drug‐resistance developing.

The regime consists of two months of isoniazid, ethambutol, rifampicin, and pyrazinamide followed by four months isoniazid and rifampicin alone.

Almost half of patients will require a surgical intervention if the disease process is not treated early. Surgical management plays a part in treating complications such as abscess formation and ureteric stricture. Nephrectomy for nonfunctioning kidneys and bladder augmentation or diversion or cystectomy for the small capacity, scarred ‘thimble’ bladder maybe required.

12.3.3.1 Introduction

Chronic pyelonephritis is the end product of recurrent or continuous inflammation of the kidney. It leads to scaring of renal tissue and permanent loss of renal function. The inflammation can be related to an infective cause such as recurrent UTIs or, as in the case of children, due to a noninfective aetiology such as vesicoureteric reflux (VUR), which leads to more marked scarring. In adults, noninfective causes are those such as high pressure retention of urine due to benign prostatic hyperplasia (BPH) or detrusor‐sphincter dysnergia in spinal cord injury, while infected causes are seen with obstructed infected uropathy (e.g. obstructive stone).

12.3.3.2 Clinical Presentation

Most patients are asymptomatic unless they show signs of recurrent UTI. Due to the insidious nature of the disease, patients may present with symptoms of end‐stage renal failure.

12.3.3.3 Investigations

The diagnosis can be made from radiological appearances and also pathological analysis. Baseline renal function must be performed followed by radiological investigations to confirm the diagnosis. Ultrasound, CT, intravenous urogram (IVU), or radioisotope imaging (DMSA) will show renal scarring, deformed calyces, and thinning of the renal cortex. Scars are typically in the upper or lower poles because these are more prone to reflux. The affected kidney may also look atrophic or shrunken on scanning.

12.3.3.4 Management

Treating the underlying cause may help prevent loss of further renal function. Optimization of renal function is imperative, and a nephrologist is required to monitor these patients. Patients with end‐stage renal failure should be considered for renal transplant or dialysis. In children, prompt assessment of VUR is required.

12.3.3.5 Complications and Prognosis

End‐stage renal failure is the only associated complication if bilateral disease.

12.5.1.1 Introduction

Retroperitoneal fibrosis (RPF) was first described by Ormond in 1948 [39], this condition is defined by fibro‐inflammatory tissue encasing the abdominal aorta and iliac vessels, which can involve the ureters. Its incidence is thought to be 1.38 per 100 000 of the population in the fifth or sixth decade of life; men are twice as commonly affected as women [40]. RPF is part of a disease spectrum known as chronic periaortitis, which is a large vessel arteritis [41]. Long‐term management of this disease is undertaken by rheumatologists and nephrologists, but urological input is required to assist in drainage of the upper tracts.

12.5.1.2 Aetiology and Pathophysiology

RFP can be idiopathic (IRPF) or secondary. Though coined ‘idiopathic’, the likelihood is that it is an autoimmune process called ‘periaortitis’. Commonly associated secondary causes are iatrogenic or traumatic (e.g. surgery, radiotherapy, or chemotherapy), tumour or malignant process (lymphoma being the most common followed by metastatic disease), infection like TB, and drugs such as beta‐blockers, hydralazine, haloperidol, amphetamine, LSD, and even methyl methacrylate cement (used in joint replacement surgery). It can be associated with autoimmune disease such as Crohn disease or Riedell thyroiditis or associated with vascular disease or treatments, abdominal aortic aneurysm, angioplasty, or intravascular stenting.

The most common cause found in more than 60% of patients is periaortitis. Inflammatory response to the leakage of insoluble lipids through the arterial wall from the atheromatous plaque leads to the formation of the fibrous whitish plaque that can extend to the ureters, pelvic organs, and retroperitoneal structures. Histologically there are chronic inflammatory infiltrates made up of macrophages, eosinophils, plasma cells, and lymphocytes; the central plaque is formed of fibrous scar tissue, while the growing periphery is active chronic inflammation. There are myofibroblasts and type 1 collagen within the fibrotic component [42].

12.5.1.3 Clinical Presentation

Clinical manifestations can be variable. Patients may present earlier on with nonspecific symptoms such as back and abdominal pains, loss of appetite or weight, night sweats, and malaise. If ureteric involvement is present, then patients may have colicky type symptoms. Late presentation is of symptoms of renal failure (acute or chronic) due to ureteric obstruction. New onset hypertension might be the only symptom. Scrotal swelling, hydroceles, and varicoceles can also occur, depending on the extent of the plaque and the vascular and lymphatic segments involved [42].

12.5.1.4 Investigations

There are no set diagnostic criteria for RPF, and the diagnosis is usually made after exclusion of other diagnoses, such as malignancy, have been ruled out. Multiple imaging modality might be needed to establish diagnosis as well as plan and follow up treatment (Figures 12.17 and 12.18).

Baseline renal function and full blood counts including inflammatory markers. ESR is elevated in the majority of cases. CT and radioisotope scanning (MAG3 or DMSA) will help to determine drainage and function of the kidneys. Retrograde pyelogram can also be used to assess narrowing and obstruction of the ureters.

CT‐guided biopsy of the RPF mass confirms diagnosis; however, a negative result for cancer does not exclude it.

MRI scanning can be used to track progression and remission of the disease. On T2‐weighted sequences hyper‐intensity can correlate with disease activity.

Other imaging modalities used are F‐fluorodeoxyglucose (FDG), positron emission tomography (PET), and CP3 67gallium (Ga) scintigraphy [43].

12.5.1.5 Management

Aims of treatment are to relieve ureteric obstruction, preserve renal function, and halt or reverse disease progression.

Relief of ureteric obstruction is a priority to preserve renal function. This can either be achieved with percutaneous nephrostomy placement (with or without anterograde stenting) or retrograde double‐J stents [42, 44, 45].

Treatment of the underlying causes is critical, but in the case of IRPF, medical management is now the mainstay of treatment and should be started as soon as possible. In cases refractory to these measures, ureterolysis and omental wrapping of the ureters will be required.

12.5.1.5.3 Ureterolysis

This can be done by either open, laparoscopic, or robotic approaches, depending on the surgeon’s experience. The colon is reflected off the ureter first on one side and then the other (Figure 12.19). The plane of cleavage between the ureter and the surrounding sheath of fibrous tissue is dissected away, liberating the ureter (Figure 12.20).

This is sometimes very difficult because the fibrosis actually penetrates the muscular wall of the ureter, and when the lumen is breached, a nephrostomy is a mandatory precaution if one is not already in position. If the injury is small, it can be left to heal with a stent in situ; however, if extensive ureteric segment is damaged, primary anastomosis, ureteric reimplantation, or even nephrectomy might be required. To prevent a return of the fibrosis, it is safest to wrap each ureter in omentum (Figure 12.21).

12.5.1.5.4 Prognosis

Whether the ureters have been placed in the peritoneal cavity or wrapped in omentum, it is necessary to follow the patient carefully. Recurrence of the fibrosis is always a possibility, and so is a new manifestation of the fibrosis in the mediastinum or porta hepatis. Fortunately, a very useful index of return of active disease is provided by the sedimentation rate. This, and the blood pressure, should be monitored indefinitely in view of the long‐term risk of atherosclerotic disease. Permanent upper tact decompression may be necessary.