Forgotten but not gone in rural South Africa: Urinary schistosomiasis and implications for chronic kidney disease screening in endemic countries.

Background: Urinary schistosomiasis caused by infection with Schistosoma haematobium ( S. haematobium) remains endemic in Africa and is associated with haematuria and albuminuria/proteinuria. Kidney Disease Improving Global Outcomes clinical guidelines recommend evaluating proteinuria/albuminuria and glomerular filtration rate for chronic kidney disease (CKD) diagnosis. The guidelines are informed by population data outside of Africa but have been adopted in many African countries with little validation. Our study aimed to characterise the burden of urinary schistosomiasis in rural South Africa (SA) and evaluate its relationship with markers of kidney dysfunction with implications for CKD screening. Methods: In this population-based cohort study, we recruited 2021 adults aged 20 - 79 years in the Mpumalanga Province, SA. Sociodemographic data were recorded, urinalysis performed, and serum creatinine and urine albumin and creatinine measured. Kidney dysfunction was defined as an estimated glomerular filtration rate (eGFR) <60ml/min/1.73m 2 and/or urine albumin-creatinine ratio >3.0mg/mmol. S . haematobium infection was determined by urine microscopy. Multivariable analyses were performed to determine relationships between S. haematobium and markers of kidney dysfunction. Results: Data were available for 1226 of 2021 participants. 717 (58.5%) were female and the median age was 35 years (IQR 27 - 47). Prevalence of kidney dysfunction and S. haematobium was 20.2% and 5.1% respectively. S. haematobium was strongly associated with kidney dysfunction (OR 8.66; 95% CI 4.10 - 18.3) and related to albuminuria alone (OR 8.69; 95% CI 4.11 - 18.8), with no evidence of an association with eGFR <90ml/min/1.73m 2 (OR 0.43; 95% CI 0.05 - 3.59). Discussion: The strong association between urinary schistosomiasis and albuminuria requires careful consideration when screening for CKD. Screening for, and treatment of, schistosomiasis should be a routine part of initial work-up for CKD in S. haematobium endemic areas. Urinary schistosomiasis, a neglected tropical disease, remains a public health concern in the Mpumulanga province of SA.

Chronic kidney disease (CKD) and associated risk in rural South Africa: a population-based cohort study.

Background: In Africa, true prevalence of chronic kidney disease (CKD) is unknown, and associated clinical and genetic risk factors remain understudied. This population-based cohort study aimed to investigate CKD prevalence and associated risk factors in rural South Africa. Methods: A total 2021 adults aged 20-79 years were recruited between 2017-2018 from the Agincourt Health and Socio-Demographic Surveillance System in Bushbuckridge, Mpumalanga, South Africa. The following were collected: sociodemographic, anthropometric, and clinical data; venous blood samples for creatinine, hepatitis B serology; DNA extraction; spot urine samples for dipstick testing and urine albumin: creatinine ratio (UACR) measurement. Point-of-care screening determined prevalent HIV infection, diabetes, and hypercholesterolemia. DNA was used to test for apolipoprotein L1 ( APOL1) kidney risk variants. Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to diagnose CKD as low eGFR (<60mL/min/1.73m 2) and /or albuminuria (UACR ≥ 3.0mg/mmol) confirmed with follow up screening after at least three months. eGFR was calculated using the CKD-EPI (creatinine) equation 2009 with no ethnicity adjustment. Multivariable logistic regression was used to model CKD risk. Results: The WHO age-adjusted population prevalence of CKD was 6.7% (95% CI 5.4 - 7.9), mostly from persistent albuminuria. In the fully adjusted model, APOL1 high-risk genotypes (OR 2.1; 95% CI 1.3 - 3.4); HIV infection (OR 1.8; 1.1 - 2.8); hypertension (OR 2.8; 95% CI 1.8 - 4.3), and diabetes (OR 4.1; 95% CI 2.0 - 8.4) were risk factors. There was no association with age, sex, level of education, obesity, hypercholesterolemia, or hepatitis B infection. Sensitivity analyses showed that CKD risk factor associations were driven by persistent albuminuria, and not low eGFR. One third of those with CKD did not have any of these risk factors. Conclusions:  In rural South Africa, CKD is prevalent, dominated by persistent albuminuria, and associated with APOL1 high-risk genotypes, hypertension, diabetes, and HIV infection.

Evaluating chronic kidney disease in rural South Africa: comparing estimated glomerular filtration rate using point-of-care creatinine to iohexol measured GFR.

OBJECTIVES: The prevalence of chronic kidney disease is rising rapidly in low- and middle-income countries. Serum creatinine and estimation of glomerular filtration rate (GFR) are critical diagnostic tools, yet access to centralised laboratory services remains limited in primary care resource-limited settings. The aim of this study was to evaluate point-of-care (POC) technologies for serum creatinine measurement and to compare their performance to a gold standard measurement using iohexol measured GFR (mGFR). METHODS: POC creatinine was measured using iSTAT® and StatSensor® devices in capillary and venous whole blood, and laboratory creatinine was measured using the compensated kinetic Jaffe method in 670 participants from a rural area in South Africa. GFR estimating equations Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease (CKD-EPI and MDRD) for POC and laboratory creatinine were compared to iohexol mGFR. RESULTS: Calculated GFR for laboratory and POC creatinine measurements overestimated GFR (positive bias of 1.9-34.1 mL/min/1.73 m2). However, all POC devices had less positive bias than the laboratory Jaffe method (1.9-14.7 vs. 34.1 for MDRD, and 8.4-19.9 vs. 28.6 for CKD-EPI). Accuracy within 30% of mGFR ranged from 0.56 to 0.72 for POC devices and from 0.36 to 0.43 for the laboratory Jaffe method. POC devices showed wider imprecision with coefficients of variation ranging from 4.6 to 10.2% compared to 3.5% for the laboratory Jaffe method. CONCLUSIONS: POC estimated GFR (eGFR) showed improved performance over laboratory Jaffe eGFR, however POC devices suffered from imprecision and large bias. The laboratory Jaffe method performed poorly, highlighting the need for laboratories to move to enzymatic methods to measure creatinine.

Diagnostic accuracy of semiquantitative point of care urine albumin to creatinine ratio and urine dipstick analysis in a primary care resource limited setting in South Africa.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is predicted to rise over the next few decades. In resource-limited settings access to central laboratory services is limited. Point-of-care (POC) urine dipstick testing offers the potential to detect markers of kidney damage (albuminuria) as well as markers of other disease processes. We evaluated the diagnostic accuracy of the semi-quantitative albumin-creatinine ratio (ACR) Sysmex UC-1000 POC urine dipstick system as well as the extent of other abnormal dipstick findings in urine. METHODS: 700 participants from a rural area in South Africa were screened for albuminuria. A spot urine sample was used to measure POC and central laboratory ACR. We determined the sensitivity, specificity, positive predictive value and negative predictive value of the POC ACR, and recorded dipstick parameters. RESULTS: The prevalence of albuminuria was 11.6% (95%CI; 9.3-14.2). Those with albuminuria had higher mean diastolic (82 vs 79 mmHg, p = 0.019) and systolic (133 vs 128 mmHg, p = 0.002) blood pressures and a higher proportion of diabetes mellitus (17.6 vs 4.9%, p < 0.001). The sensitivity of the POC ACR system was 0.79, specificity 0.84, positive predictive value 0.39 and negative predictive value 0.97. The sensitivity improved to 0.80, 0.85, 0.85 and 0.89 in those with elevated blood pressure, diabetes mellitus, HIV positive status, and those 65 years and older, respectively. Abnormalities other than albuminuria were detected in 240 (34.3%) of the samples; 88 (12.6%) were positive for haematuria, 113 (16.1%) for leucocytes, 66 (9.4%) for nitrites and 27 (3.9%) for glycosuria. CONCLUSION: Our study shows that POC ACR has good negative predictive value and could be used to rule out albuminuria when screening for CKD. Additionally, a high proportion of participants had other urine abnormalities detected with dipsticks which may reflect kidney disease or co-morbid untreated genitourinary pathology such as urinary tract infections or endemic schistosomiasis with important implications for CKD.