In most African countries, limited resources and health infrastructure are associated with late presentation and poor recognition and treatment of AKI. In studies reporting dialysis need, 66% of children and 70% of adults had indications for dialysis but only 64% and 33% of these patients received dialysis, respectively. The mortality was 73% in children and 86% in adults when dialysis was needed but not received. Major barriers to access to care were unaffordable out-of-pocket costs, limited hospital resources, late presentation, and female sex. In another review of AKI in Nigerian children between 1990 and 2012, dialysis access rates ranged between 15% and 68% of those with an indication for dialysis. In North Africa, dialysis for AKI is more easily accessible in hospital settings. In a Moroccan survey, dialysis was needed in 40% of cases and intermittent hemodialysis was the predominant treatment modality. In-hospital mortality was 25%, dialysis dependence was 7%, residual kidney failure was present in 39%, and complete recovery was documented at 29%.

Two global initiatives have impacted the outcomes of patients with AKI, especially in low-resource settings. In 2013, the ISN launched “0by25,” an ambitious initiative to eliminate preventable deaths from AKI by 2025. The project focuses on evidence and awareness, as well as on training for health workers to increase the early detection of AKI and appropriate use of simple management, such as fluid repletion. The second initiative is “Saving Young Lives,” which aims to develop acute peritoneal dialysis programs in low-resource settings. ^, Peritoneal dialysis can be lifesaving in treating AKI where hemodialysis is not available. Locally prepared peritoneal dialysis fluid adapted from commonly available intravenous solutions can be used safely and effectively. Practical hands-on training covering all aspects of acute peritoneal dialysis has already been provided to 69 nurses and 209 doctors at an annual training course held at the Red Cross War Memorial Children’s Hospital in Cape Town, South Africa.

Importantly, a large proportion of AKI cases and their clinical consequences are potentially preventable. Education regarding the avoidance of nephrotoxins, prompt treatment of infections, and fluid replacement are important facets of therapy, especially in countries with limited access to kidney replacement therapies.

The Africa region is projected to experience the highest growth rates in the number of people with diabetes, with the total number increasing by 129% to 55 million by 2045. These increases are driven by sedentary lifestyles, unhealthy diets, obesity, population growth, and aging.

Noubiap and colleagues included 32 studies in a systematic review of diabetic nephropathy in Africa. The reported prevalence varied from 11% to 83.7%. The rate of ESKF at 5 years of follow-up was 34.7%, and the mortality rate from diabetic nephropathy was 18.4% at 20 years of follow-up. More recently, Wagnew and colleagues performed a meta-analysis to estimate the prevalence of diabetic nephropathy in sub-Saharan Africa. Most of the 27 included studies used proteinuria as evidence of nephropathy, and one-third were conducted in patients with type 2 diabetes mellitus. The pooled prevalence of diabetic nephropathy was 35.3%. The prevalence was highest in patients with type 2 diabetes mellitus (41.4%) and in the Southern African region (40.4%).

A systematic review by Ajayi and colleagues assessed the prevalence of CKD from studies in Africa reporting target organ damage related to hypertension. The review included 12 studies (5297 participants) from six African countries: Ghana, Nigeria, Uganda, Tanzania, the Democratic Republic of the Congo, and South Africa. The overall prevalence of CKD among hypertensive patients was 18%, with the highest prevalence observed in West Africa (21%) and urban areas (20%). In registry reports from South Africa, Ghana, and Egypt, hypertension was reported as the etiology of kidney failure in 34% to 41% of patients on KRT ( Table 75.2 ). Unpublished data from Kenya and Senegal also highlight hypertensive kidney disease as a leading cause of kidney failure.

It is generally accepted that accelerated and malignant forms of hypertension can lead to kidney failure, ^, although recovery of kidney function sometimes occurs months after starting KRT, especially when patients are treated with peritoneal dialysis. In a study published in 1982, Gold and colleagues reviewed the renal histology in 65 Black South African patients on chronic hemodialysis and reported that primary malignant hypertension was the most common cause, occurring in 49%. Large South African biopsy series have been published more recently, reporting hypertensive kidney disease in only 1.3% (Cape Town, 2227 biopsies) and 6.2% (Johannesburg, 1848 biopsies) of their biopsies, respectively.

Nephrologists also often apply a diagnosis of “hypertensive kidney disease” or “hypertensive nephrosclerosis” to nondiabetic patients, especially Black patients, who present with CKD and only mild-to-moderate hypertension. It now seems clear that many of these patients have glomerular disease, which is related to the presence of renal-risk variants of the APOL1 gene, and have secondarily elevated blood pressure. For example, in the African American Study of Kidney Disease and Hypertension, the APOL1 association was strongest in individuals with more proteinuria and progressive nephropathy. Aggressive hypertension control and the use of angiotensin-converting enzyme inhibitors failed to halt progression, supporting the role of mechanisms other than hypertension. The American Study of Kidney Disease and Hypertension patients predominantly had focal glomerulosclerosis with interstitial and vascular changes that did not correlate with blood pressure. This information prompted calls for the term “hypertensive nephrosclerosis” to be abandoned. ^,

The South African Renal Registry recommends that its users submitting data indicate hypertensive kidney disease as the primary diagnosis only if there is no reason to suspect that the hypertension may be secondary to preexisting kidney disease, according to the following criteria: hypertension known to precede kidney dysfunction, left ventricular hypertrophy, proteinuria <2 g/day and no evidence of other kidney diseases. ^,

Okpechi and colleagues conducted a systematic review of histologically proven glomerulonephritis in Africa between 1980 and 2014. They noted declining kidney biopsy rates and the consequent paucity of data on pathologic patterns of kidney diseases from Africa. Of the 24 studies (12,093 biopsies) from 13 countries, 70% originated from North African countries. Nephrotic syndrome was the most common indication for kidney biopsy. Minimal change disease represented 16.5%, focal segmental glomerulosclerosis (FSGS) 15.9%, mesangiocapillary glomerulonephritis (MCGN) 11.8%, membranous nephropathy 6.6%, IgA nephropathy 2.8%, and crescentic glomerulonephritis 2.0% of the primary kidney diseases. Nephritis related to hepatitis B (8.4%) and systemic lupus erythematosus (7.7%) had the highest prevalence among secondary glomerular diseases. Fig. 75.9 illustrates some of the differences between North African and sub-Saharan African countries.

Esmail and colleagues reviewed 2227 native kidney biopsies performed at a tertiary center in Cape Town, South Africa, over 22 years. The most common primary glomerular disease was MCGN (34.5%), followed by FSGS (22.3%) and membranous nephropathy (15.8%). Lupus nephritis was the most common secondary glomerular disease (39.1%), followed by HIV-associated nephropathy (HIVAN) (22.1%). Vermeulen and colleagues published a series of 1848 native kidney biopsies performed more than 30 years in Johannesburg, South Africa, and reported FSGS as the most common primary glomerular disease (29.6%), followed by membranous nephropathy (25.7%) and MCGN (18.1%). Lupus nephritis (31%) and HIVAN (13.3%) were also the most common secondary glomerular diseases identified.

Following the introduction of the new classification for MCGN, there has been a dearth of data on C3 glomerulonephritis from Africa. A recent study by Hargey and colleagues reported on the outcomes of 19 patients with C3 glomerulonephritis in Cape Town, South Africa. During a median follow-up period of 15 months, nearly 80% of the patients had experienced the composite outcome of CKD, ESKF, or death.

Uwaezuoke and colleagues conducted a systematic review to investigate the most common histopathologic diagnoses in steroid-resistant childhood nephrotic syndrome in sub-Saharan Africa. Four of the included studies were from Nigeria, and two from South Africa. The most common diagnoses were FSGS (57.2%), MCGN (22.4%), minimal change disease (14%), and membranous nephropathy (6.7%).

Glomerular diseases also common in Africa include postinfectious glomerulonephritis and those associated with lupus, hepatitis B, and schistosomiasis. These conditions are discussed in detail elsewhere in this book.

According to the 2022 UNAIDS Global AIDS Update, progress toward ending the AIDS pandemic is slowing rather than accelerating. The COVID-19 pandemic and economic and humanitarian crises have placed the global HIV response under increasing threat.

Eastern and Southern Africa remain the regions of the world with the heaviest burden of infection. In 2022, 20.8 million people in these regions were living with HIV, there were 500,000 new HIV infections, and there were 260,000 HIV-related deaths. The proportion of patients who were on treatment was 83%. Some African countries have already achieved the 95–95–95 targets (95% of people living with HIV know their HIV status, 95% of those receive sustained ART, and 95% of people receiving ART have viral suppression). These include Botswana, Eswatini, Rwanda, Tanzania, and Zimbabwe. An additional eight sub-Saharan African countries are also close to doing so.

A broad spectrum of kidney diseases is seen in patients with HIV infection. This includes diseases directly related to the HIV infection, those related to superinfections, those related to the immune response, and those related to the treatment. HIVAN is the classic lesion described, presenting with nephrotic-range proteinuria and decreased renal function but, because of renal salt wasting, patients often do not have hypertension or significant edema. Renal histology reveals a collapsing form of FSGS, with associated cystic tubular dilatation, interstitial inflammation, and the presence of tubuloreticular inclusion bodies. HIV RNA has been demonstrated in podocytes and tubular epithelial cells.

HIVAN was first reported in 1984, with the first reports from Africa published in the late 1980s and early 1990s. The worldwide prevalence is highest in sub-Saharan Africa, occurring especially in the absence of ART and in patients with markedly reduced CD4 counts and elevated viral loads.

Individuals of African descent have a genetic susceptibility to the development of HIVAN that is related to single nucleotide polymorphisms in the apolipoprotein L1 (APOL1) gene. The G1 variant includes two missense mutations ( S342G , Rs73885319 and I384M , Rs60910145 ) that are in close linkage disequilibrium, and the G2 variant is a two-base pair deletion ( N388del, Y389del, Rs71785313 ). These variants confer risk for HIVAN and HIV-associated FSGS, as well as other glomerular diseases and hypertensive nephrosclerosis. Kasembeli and colleagues have demonstrated that HIV-positive, ART-naïve Black South Africans with two APOL1 risk alleles are at high risk for developing HIVAN. In their study, 79% of patients with HIVAN and only 2% of controls carried two risk alleles. Individuals carrying any combination of two risk alleles had 89-fold higher odds of developing HIVAN compared with HIV-positive controls. It is estimated that 50% of HIV-positive individuals who have two APOL1 risk alleles and do not receive effective ART will develop HIVAN.

There is wide variability in the prevalence of HIVAN in different African populations. This is likely to be related to the frequency of APOL1 risk alleles. The highest frequency of the G1 and G2 variants is found in West Africa, while populations in North and East Africa have a much lower frequency of the risk alleles and of HIV-related kidney disease. For example, in Kenya, Koech and colleagues performed kidney biopsies on ART-naïve, HIV-positive adults who had persistent proteinuria. None of the biopsies revealed HIVAN; acute interstitial nephritis was the most common histologic diagnosis in this group of patients.

Kidney biopsy data on African patients with HIV infection have mostly come from South African studies. In Durban, Han and colleagues biopsied 30 patients with proteinuria who were not on ART and found that 83% had HIVAN. Gerntholtz and colleagues described the findings in 99 patients from the Johannesburg area; 27% of the biopsies showed classic HIVAN, 21% had HIV-related immune complex disease (HIV-ICD), and more than half had diagnoses that were not directly related to the HIV infection. Also from Johannesburg, the biopsy series of Vermeulen and colleagues included 364 HIV-infected patients; HIVAN was present in 32.7% and HIV-ICD in 11.8% of these patients. Wearne and colleagues reviewed the biopsies of 192 HIV-infected patients in Cape Town, reporting that HIVAN was the most common histologic diagnosis (57%), with the collapsing subtype of FSGS present in 43%. Immune complex disease was present in 8.3% and a combination of HIVAN and HIV-ICD in 21.9%. The biopsy series of Esmail and colleagues, from Cape Town, included 504 HIV-infected patients. The most common pathology in these patients was HIVAN (44.2%), followed by acute tubular necrosis (40.1%). Many patients had more than one histopathologic diagnosis.

Wearne and colleagues (in 671 biopsies) and Diana and colleagues (690 biopsies) have described a shift in the spectrum of kidney disease among HIV-infected South Africans since the introduction of ART in 2004. Tubulointerstitial disease has become more prevalent, possibly related to factors such as tuberculosis, sepsis, and tenofovir use, whereas there has been a decrease in the prevalence of classic HIVAN. Diana and colleagues also reported an increase in the prevalence of FSGS (not otherwise specified). Kidney outcomes were poorest in patients with HIVAN, possibly related to late presentation.

The widespread use of ART has led to substantial reductions in the incidence of HIVAN and HIVAN-related kidney failure, but there have been conflicting reports on the benefit of ART in patients with HIV-ICD. Szczech and colleagues reported that lesions other than HIVAN did not benefit from ART. Several African studies have demonstrated improvements in kidney function in patients who have initiated ART for HIV-related kidney disease. These include the DART study in Uganda and Zimbabwe, the study by Peters and colleagues in Uganda, the study by Mpondo and colleagues in Tanzania, and the South African studies by Wearne and colleagues in Cape Town and Fabian and colleagues in Johannesburg. The South African studies included kidney biopsy data and, unlike the study by Szczech and colleagues, demonstrated benefits in both HIVAN and HIV-ICD. In contrast, Inusah and colleagues found that HIV infection had no impact on kidney outcomes in patients with immune complex MCGN. The authors suggested that ART was unlikely to influence the kidney outcomes in the light of their patients’ late presentation and severe histopathological findings.

North African countries lie within a geographic Afro-Asian stone-forming belt where kidney stone disease is particularly common. In this region, all age groups are affected, with a male predominance. The high prevalence of urolithiasis may be related to high rates of consanguinity, hot climates, and dietary factors such as high intake of animal protein.

Conversely, sub-Saharan Africa has the lowest incidence of kidney stones compared with other regions worldwide. Contributing factors include reduced genetic predisposition, a younger population living in rural areas with lower ambient temperatures, less sedentary lifestyles, and lower rates of obesity. Moreover, diets tend to be rich in micronutrients with less protein and sugar and there is less use of lithogenic medications like acetazolamide, lithium, warfarin, calcium, and vitamin D supplements.

Kaestner and colleagues examined the prevalence of metabolic abnormalities in 175 patients attending a kidney stone clinic in Cape Town, South Africa. The main abnormalities were hypocitraturia (61%), hypomagnesuria (41%), mild hypercalciuria (22%), and hyperuricosuria (20%). In 432 Moroccan children, Meiouet and colleagues found that calcium oxalate stones were the most prevalent (52%) followed by struvite (18%), ammonium urate (10%), and carbapatite stones (9%). Calcium oxalate accounted for 72% of stones in girls and 43% in boys; struvite stones were more frequent in boys than in girls (22% vs. 9%), as were calcium phosphate stones (12% vs. 4.6%).

There is a paucity of African data on CKD or kidney failure resulting from kidney stone disease. In Tunisia, 2.7% of patients on chronic dialysis have stones as the etiology. In Sudan, 10% to 12% of patients on dialysis have obstructive uropathy as the etiology of their kidney failure. ^, In Libya, the prevalence was 5% and in Egypt it was 4% for stones and 2% for obstructive uropathy. In South Africa, only 1.7% of patients on KRT had obstruction and/or reflux as the primary kidney disease. There were few patients for whom there was specific mention of calculi, uric acid nephropathy, cystinosis, hyperoxaluria, or hypercalcemia.

Africa carries approximately 75% of the global burden of sickle cell disease, mainly due to a high prevalence of sickle cell trait in West Africa. It is estimated that 25% of Nigerian adults are carriers. The presence of sickle cell trait protects against the severe complications of Plasmodium falciparum malaria, which is endemic in the region.

Kidney involvement is common and more severe in homozygous disease (sickle cell anemia, HbSS) than in the compound heterozygous forms; however, even sickle cell trait is associated with increased risk of CKD. The renal involvement contributes to a diminished life expectancy, accounting for 16% to 18% of the mortality. Even patients who are able to access KRT have a mortality rate several-fold higher than patients without sickle cell disease.

Several gene variants have been implicated in the development of sickle cell nephropathy including HBA1, HBA2, APOL1, HMOX1, and ACKR1 . Hemolysis, vaso-occlusion, and ischemia-reperfusion injury are the mechanisms underlying the clinical manifestations of sickle cell disease. The pathophysiology of the renal involvement involves the coexistence of cortical hyperperfusion, medullary hypoperfusion, and an increased vasoconstrictive response to systemic and regional stress. Red blood cells sickle in the renal medulla because of its hypoxic, acidotic, and hyperosmolar conditions.

Clinical manifestations range from hematuria and loss of concentrating ability to acute kidney injury, CKD, and renal medullary carcinoma. The most common glomerular lesion is FSGS. Hyperfiltration and impaired concentrating ability may occur in infancy, albuminuria may develop in childhood and progress thereafter, and in older adults the risk of CKD and kidney failure increases. Hematuria and AKI can occur at any age. Hypertension was previously considered uncommon in patients with sickle cell disease, but more recent evidence suggests that its prevalence may be higher, with reported rates reaching 19%.

A Nigerian case series by Arogundade and colleagues reported that 37% of their patients with sickle cell disease had CKD as defined by persistent proteinuria, hematuria, and/or reduction in GFR. Another Nigerian study, among 200 stable patients, reported that 54% had albuminuria and only 6% had both albuminuria and an eGFR <60 mL/min per 1.73 m ² . In the Democratic Republic of Congo, a study of 98 stable patients found that 87% had albuminuria and only 4% had a low GFR.

Established therapies include hydroxyurea and red blood cell transfusions, as well as inhibitors of the renin-angiotensin-aldosterone system (RAS). A systematic review published in 2021 identified only one randomized controlled trial and concluded that there was not enough evidence that RAS inhibitors reduce proteinuria in people with sickle cell disease. Due to the risk of sickling crisis caused by potential hypovolemia, diuretics are typically avoided as a treatment option. When managing anemia, erythropoiesis-stimulating agents can safely be used in conjunction with hydroxyurea. Recently, several newer therapies have been approved for use in sickle cell disease including L-glutamine, pyruvate kinase inhibitors, and gene therapies using modified autologous stem cells.

Data on African patients with sickle cell disease receiving KRT are limited. The Ghanaian Renal Registry reported that only 0.3% of treated patients had sickle cell disease. Dialysis does not appear to increase the risk of vasoocclusive crisis, but there is an increased risk of vascular access failure, possibly related to coagulopathy and endothelial dysfunction. When performing hemodialysis, avoiding excessive ultrafiltration, using low dialysate temperatures, and using high dialysate sodium concentrations may reduce the risk of vaso-occlusive crises. Peritoneal dialysis may be the preferred treatment modality as it avoids the need for vascular access for dialysis and reduces the risk of excessive volume depletion. Kwarteng-Siaw and colleagues have reported a survival advantage for patients treated with peritoneal dialysis. Kidney transplantation for patients with sickle cell disease remains a viable option, with survival rates comparable with those of patients with diabetes.

Participation of Africans in genomics research has been limited, with reasons for this including a shortage of African scientists with genomic research expertise, lack of research infrastructure, limited computational expertise and resources, and inadequate support by governments. Adedokun and colleagues analyzed genetics publications from sub-Saharan Africa for the period 2004–2013 and found that most of the publications involved populations from South Africa (31.1%), Ghana (10.6%), and Kenya (7.5%). Less than half of the publications had a first author from an African institution. Ilori and colleagues have reviewed genetics research in low-resource settings and reported that only 5% of genome-wide association studies (GWAS) have been conducted in low-resource settings, which are home to nearly 60% of the world’s population. Africans represent only 8.7% of all publicly available next-generation sequencing data, despite accounting for 15.4% of the world’s population.

The Human Heredity and Health in Africa (H3Africa,

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) initiative is a large-scale collaboration between the U.S. National Institutes of Health, the U.K.-based Wellcome Trust, and the African Society of Human Genetics, which has begun to address some of these issues by focusing strongly on capacity building, as well as specific scientific goals. The project is training African clinical research personnel and genomic investigators, establishing genomic research laboratories, and conducting international-level genetic and translational research. Three biorepositories have been established in Nigeria, Uganda, and South Africa for DNA and other biosamples. The H3Africa Kidney Disease Research Network (H3AKDRN) studies the genetic and environmental factors associated with CKD including the role of the African “risk” variants of the APOL1 gene and genetic factors involved in sickle cell disease. H3AKDRN has recruited more than 10,000 patients and healthy controls in Ghana, Nigeria, Ethiopia, and Kenya. ^, Of these, 3000 have had a GWAS using the new H3Africa Illumina chip and 750 have had kidney biopsies. So far, they have discovered that participants carrying two APOL1 risk alleles have a 45% higher risk of developing CKD compared with those with one or no risk alleles. Nearly one-quarter of healthy controls from Ghana and Nigeria carry the two risk alleles, and one-third of participants with CKD carry these same alleles.

The Role of Consanguineous Marriage

A consanguineous marriage is defined as a union between two individuals who are related as second cousins or closer. This practice is common throughout Arab countries and contributes to the increase in genetic disorders, especially autosomal recessive disorders, seen in North Africa (see Chapter 76 ). For example, the high rates of kidney stone disease seen in the region are at least partly due to consanguinity, which results in higher rates of predisposing conditions such as primary hyperoxaluria and cystinosis. Jaouad and colleagues studied the rates of consanguineous marriages in 176 Moroccan families with autosomal recessive diseases. While the overall prevalence of consanguinity in Morocco was reported to be 15%, the rate among the families with autosomal recessive disorders was 59%.

Cystic Kidney Disease

Worldwide, autosomal dominant polycystic kidney disease (ADPKD) is a common cause of CKD and kidney failure, but the data from African populations are sparse. Bourqia reported data on ADPKD in 308 Moroccan families. The mean age at diagnosis was 46 years, and pain was the most frequent presenting symptom. Loss of kidney function was present in 17% and hepatic cysts in 18%. In Benin, Laleye and colleagues described 70 patients with a mean age of 47 years. A positive family history was obtained in 47%, and flank pain was the most common presenting symptom. Mutations in the polycystin 1 gene ( PKD1 ) were identified including several variants not previously described. In Senegal, a cohort of 53 patients has been described, as has a case where a new PKD1 mutation was identified. A Ghanaian study of 82 patients reported flank pain (31%) and leg swelling (18%) as the most common symptoms. CKD was present in 82% of the patients, with 20% having stage 5 CKD. In Nigeria, 41 patients with ADPKD were seen over a 15-year period. Nocturia (78%) and flank pain (68%) were common symptoms, and a family history of ADPKD was present in 56%. Liver cysts (32%) and aortic regurgitation (22%) were the predominant extrarenal manifestations. The median eGFR was 34 mL/min per 1.73 m ² at presentation, and many progressed to kidney failure, with 63% starting dialysis. In the Seychelles, ADPKD has been seen almost exclusively in people of Caucasian extraction, even though they comprise only 30% of the population. This may be the consequence of a founder effect.

Autosomal recessive polycystic kidney disease (ARPKD) is caused by mutations in the PKHD1 gene and has a worldwide incidence of 1:20,000, corresponding to a heterozygote frequency of 1:70. Among the Afrikaner population of South Africa, the live-birth rate and carrier rate have been estimated at 1:11,000 and 1:53, respectively. Lambie and colleagues studied a cohort of patients from 36 Afrikaner families, finding that 27 patients, from 24 families, were homozygous for the p.M627K substitution, providing strong evidence of a founder mutation.

Nephronophthisis (NPHP) is an autosomal recessive cystic kidney disease that is a leading genetic cause of kidney failure in children. In contrast to ADPKD, the kidneys are not enlarged, cysts are present mostly at the corticomedullary junction, and there is prominent tubulointerstitial fibrosis. Soliman and colleagues studied 20 Egyptian children with NPHP, reporting a mean age at diagnosis of 88 months and a mean age at the onset of symptoms of 44 months. Patients were categorized as 75% juvenile NPHP, 5% infantile NPHP, and 20% Joubert syndrome-related disorders.

Metabolic Diseases

Primary hyperoxaluria type 1 (PH1) is an autosomal recessive metabolic disease where there is increased endogenous production of oxalate (see Chapters 40 and 71 ). Progressive kidney failure results from excessive urinary oxalate excretion and renal deposition of calcium oxalate. Disease-causing mutations of the alanine glyoxylate aminotransferase ( AGXT ) gene have been identified in patients from Tunisia and Egypt.

Cystinosis is an autosomal recessive lysosomal storage disease caused by mutations in the CTNS gene. A study of 20 South African children with nephropathic infantile type cystinosis, characterized by proximal tubule dysfunction, found that 19 children had a G>A mutation in intron 11 and that 16 were homozygous for this mutation.

Hereditary tyrosinemia type 1 (HT1) is caused by a mutation that results in a deficiency of fumarylacetoacetate hydrolase, leading to tyrosine accumulation. Kidney-related manifestations include nephromegaly, nephrocalcinosis, Fanconi syndrome, kidney stones, and CKD. El-Karaksy and colleagues studied 22 affected Egyptian children and found that 64% had rickets accompanied by hypophosphatemia, while 77% had nephromegaly.

Familial Mediterranean fever is an autosomal recessive disease that primarily affects populations surrounding the Mediterranean and is characterized by recurrent attacks of fever and serosal inflammation. Amyloidosis is a serious complication of the disease and may result in renal failure. The disease is caused by mutations in the familial Mediterranean fever gene (MEFV), which encodes pyrin, a protein involved in regulating inflammatory responses. Mutations may cause gain of function so that pyrin can initiate inflammation in the absence of a toxin or infection. MEFV mutations have been identified in Tunisian patients. Amyloidosis is more common in North African patients who are homozygous for the M694V mutation, and the risk is also increased in male patients and those bearing the polymorphism a/a in the SAA1 gene.

Tubular Disorders

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by a novel claudin16 mutation has been reported in an Egyptian family. In South Africa, new mutations of the SLC12A3 gene, which encodes the sodium-chloride cotransporter on the apical membrane of the distal convoluted tubule, have been reported in a family with Gitelman syndrome who presented with hypokalemia and unusual cravings for salt and vinegar. Mutations of the epithelial sodium channel (ENaC) have also been identified in South African patients in association with hypertension ^, and preeclampsia. In Tunisia, mutations of the H ⁺ -ATPase pump have been identified in children with primary distal renal tubular acidosis, often associated with sensorineural deafness.

Glomerular Diseases

Mutations of the nephrin gene (NPHS1) have been discovered in North African patients with congenital nephrotic syndrome of the Finnish type. A Moroccan infant with steroid-resistant nephrotic syndrome had a mutation in the ARHGDIA gene, which encodes Rho-GDP dissociation inhibitor 1. This protein modulates signaling through Rho GTPases and thereby regulates cell motility.

Nandlal and colleagues examined causal genetic mutations associated with steroid-resistant nephrotic syndrome in 70 South African children. Potentially pathogenic mutations were identified in 39% of the children, with 21% carrying the NPHS2 p.V260E homozygous mutation, which is linked to biopsy-proven FSGS. Additionally, 17% of the children had heterozygous mutations involving the INF2, CD2AP, and TRPC6 genes, which have an autosomal dominant inheritance mode.

CKD of Uncertain Etiology (see also “Classification and Management of Chronic Kidney Disease”)

CKD of uncertain etiology (CKDu) describes CKD not attributable to traditional risk factors such as diabetes, hypertension, or HIV infection. CKDu “hotspots” have been reported from several African countries. For example, in Tunisia, chronic interstitial nephropathy has been linked to the contamination of food with ochratoxin, while in Tanzania, urban residence was a strong risk factor for the presence of CKD. In the El-Minia region of Egypt, kidney failure with an unknown etiology in rural farm workers has been associated with environmental factors, such as drinking unsafe water, exposure to pesticides, and using herbal medications. In Malawi, however, a study of CKDu in rural and urban adults without diabetes, hypertension, or proteinuria found a low prevalence of 0.2% (CKDu is discussed in more detail in Chapters 74 and 83 ).