Graham Paget

Infection and glomerulonephritis

Glomerular injury, occurring either as primary glomerular disease or as part of a systemic disease process, is usually a result of immune-mediated mechanisms. The morphologic reaction pattern has a diverse spectrum of appearance, ranging from normal by light microscopy in minimal change disease to crescentic forms of glomerulonephritis, with conspicuous disruption of the normal glomerular morphology. The mechanisms of glomerular immune deposit formation include trapping of circulating antigen–antibody complexes and the in situ formation of immune complexes within the glomerulus. While the majority of postinfectious immune-complex-mediated glomerulonephritides are believed to result from the deposition of circulating antigen–antibody complexes, preformed outside of the kidney and secondarily deposited in the kidney, the notion of forming in situ antigen–antibody complexes to either planted antigens or to integral structural components of the glomerulus, through “cross-reacting” autoimmune reactions, is gaining popularity in a variety of forms of glomerulonephritides. Patients with HIV infection may develop a spectrum of renal pathology, the glomerular manifestations of which include both antigen–antibody complex and nonimmune-complex-mediated pathogenetic mechanisms. Similarly, patients with Streptococcal infections, Hepatitis B virus, or Hepatitis C virus infection may develop a spectrum of glomerulonephritides, which are predominantly immune-complex-mediated. Therapy for glomerular diseases due to HIV, hepatitis B, or C virus infections remains a challenge.

Guideline for the management of nosocomial infections in South Africa.

OBJECTIVE To write a guideline for the management and prevention of nosocomial infections in South Africa in view of the following: Nosocomial infections are a common and increasing problem globally, including South Africa. Widely varying standards of prevention and management of these important infections. Increasing and emerging antimicrobial resistance among commonly isolated pathogens. The significant economic burden of these infections on the health care system as well as their impact on patient morbidity and mortality. The main aims of the guideline are to provide recommendations for the initial choice of antimicrobial agents and the appropriate management of these infections encompassing the following conditions: (i) nosocomial pneumonia, health care-associated pneumonia and ventilator-associated pneumonia; (ii) nosocomial bloodstream infections; (iii) nosocomial intravascular infections; (iv) nosocomial urinary tract infections; (v) nosocomial intra-abdominal infections; and (vi) nosocomial surgical skin and soft-tissue infections. EVIDENCE Working group of clinicians from relevant disciplines, following detailed literature review. RECOMMENDATIONS These include details of the likely pathogens, an appropriate diagnostic approach, antibiotic treatment options and appropriate preventive strategies. ENDORSEMENT The guideline document was endorsed by the South African Thoracic Society, the Critical Care Society of Southern Africa and the Federation of Infectious Diseases Societies of Southern Africa.

Uniquely South African: time to consider offering HIV-positive donor kidneys to HIV-infected renal failure patients?

Kidney transplantation has been established as the most effective form of renal replacement therapy from a cost and quality of life perspective in the developed world.

Management of patients with chronic kidney disease

Co-operation between primary healthcare workers (clinic staff and general practitioners) and nephrologists is essential and the ability to refer patients timeously should be on a pre-negotiated and organised basis. This article deals with these aspects, including follow-up guidelines and management and treatment strategies, including lifestyle changes where indicated and referral for end-stage renal failure, i.e. for dialysis and transplantation.

Utility of reticulocyte haemoglobin content and percentage hypochromic red cells as markers of iron deficiency anaemia among black CKD patients in South Africa

Introduction Iron deficiency anaemia (IDA) worsens the prognosis and outcomes of chronic kidney disease (CKD). However, while the haemoglobin level is unreliable for early detection of IDA, reticulocyte haemoglobin content (CHr) and hypochromic red cells (%HYPO) are early markers of IDA. Methods This was a cross sectional study of black adult participants (n = 258) with CKD and apparently healthy members of staff and patients’ relatives (n = 141) at the Charlotte Maxeke Johannesburg Academic Hospital, South Africa, between 1 June 2016 and 31 December 2016. Serum iron, serum ferritin and transferrin were measured using standard laboratory methods, while the haematology analyser was employed to measure CHr and %HYPO. The validity of CHr and %HYPO as markers of IDA were evaluated. Multivariable binary logistic regression was conducted to determine predictors of the relationship between IDA, CHr and %HYPO. The area under the receiver operator characteristics (ROC) curve (AUC) of the final models were utilised to evaluate the discriminatory value of CHr and %HYPO respectively. Results About one-quarter (26.1%) of the participants had IDA which was more than three times more frequent among CKD patients, compared to controls (35.3% vs 9.2%); 32.3% (95%CI: 27.90%– 37.10%) of the study population had iron deficiency without anaemia and the prevalence of iron deficiency without anaemia was lower in CKD patients compared to controls (29.5% vs 37.6%). The mean age of CKD patients was higher than in controls (52.7 ±14.3 vs 40.4 ±12.6 years, P-value<0.001). The sensitivity and specificity for diagnosing IDA among CKD participants was 62.6% and 80.2% respectively for CHr (at a cut-off value of <28pg) and 63.3% and 79.8% respectively for %HYPO. CKD participants with CHr levels >28pg were 82% less likely to be diagnosed as having IDA as compared to those with CHr levels ≤ 28pg) (adj odds ratio = 0.18, 95% CI: 0.09–0.37). The AUC of CHr (0.81, 95% CI: 0.76–0.87) was higher than the AUC of %HYPO (0.76, 95%CI: 0.70–0.82). Conclusion The diagnostic usefulness of CHr and the screening performance of %HYPO in predicting IDA among CKD patients are high. Their lower cost compared to conventional markers of ID recommend their use in clinical practice. Further cost effectiveness studies of these parameters are warranted.

Atherosclerotic vascular disease and its correlates in stable black South African kidney transplant recipients

Background Despite remarkable improvement in renal function attributable to kidney transplantation, the burden of cardiovascular disease (CVD) among kidney transplant recipients (KTRs) remains high in the post-transplant period. Aggressive use of statins in KTRs may make lipoprotein ratios correlate better with atherosclerotic vascular disease (AsVD) when compared with traditional lipid profile parameters. We therefore evaluated the clinical and echocardiographic correlates of AsVD among non-diabetic, stable, black KTRs in South Africa. Methods This was a cross-sectional study of 41 adult (18–65 years), non-diabetic, stable KTRs and 41 age- and sex-matched healthy controls. An interviewer-administered questionnaire was used to obtain information on participants’ sociodemographic and cardiovascular risk factors. Anthropometric parameters were measured. Urine and blood samples were obtained and analyzed. Echocardiography was performed and carotid intima media thickness (CIMT) was assessed in both right and left carotid arteries. Spearman’s rank correlation and binary logistic regression were performed to determine the relationship between CVD risk factors and AsVD. Results AsVD was present in 46.3% of KTRs compared to 17.1% of healthy controls (p = 0.004). Left ventricular hypertrophy was present in 92.7% of the KTRs. There were statistically significant differences in waist–hip ratio, systolic blood pressure, mean arterial pressure, urine albumin–creatinine ratio, serum fibrinogen, serum creatinine, estimated glomerular filtration rate, left atrial diameter, left ventricular mass (LVM), and left ventricular mass index (LVMI) between KTRs and controls. A positive relationship was seen between CIMT and certain risk factors for CVD including LVM, LVMI, and mitral valve deceleration time, (p < 0.001). Castelli index 2 and lipoprotein combine index (LCI) showed positive correlation with CIMT. On multivariate analysis, increasing age and kidney transplant status were independent predictors of AsVD after controlling for other risk factors. Conclusion AsVD was common among KTRs. Older age and kidney transplant status independently predicted AsVD. Castelli index 2 and LCI correlated with AsVD better than serum lipid parameters.

Racial Variations in the Markers of Mineral Bone Disorders in CKD Patients in South Africa

Introduction Several studies showed that serum intact parathyroid hormone (PTH), phosphate, and vitamin D levels differ across races. These comparative studies were largely carried out between Caucasians and black Americans. However, little is known of the existence of these associations in an African population with chronic kidney disease (CKD). Methods This cross-sectional multicenter study involved 293 CKD patients from 3 renal units in Johannesburg, South Africa. Results The 293 CKD patients (208 blacks, 85 whites) had an overall mean age of 51.1 ± 13.6 years, and black patients were significantly younger than the white patients (48.4 ± 13.6 years vs. 57.1 ± 15.5 years; P < 0.001). Compared with whites, blacks had higher median intact PTH (498 [range: 37–1084] pg/ml vs. 274 [range: 131–595] pg/ml; P = 0.03), alkaline phosphatase (122 [range: 89–192] U/L vs. 103 [range: 74–144] U/L; p = 0.03), and mean 25 OH vitamin D3 (26.8 ± 12.7 ng/ml vs. 22.7 ± 12.2 ng/ml, P = 0.01) levels, whereas their median fibroblast growth factor (FGF) level was 23 (100 [range: 34–639] pg/ml vs. 233 [range: 80–1370] pg/ml; P = 0.002), and their mean serum phosphate (1.3 ± 0.5 vs. 1.5 ± 0.5; P = 0.001) levels were significantly lower. In multivariable analyses, black race was independently associated with increased log PTH (β = 0.488, P = 0.01) and decreased log FGF-23 (β = −0.636, P = 0.02). Similarly, blacks had a 3.08 times higher likelihood (95% confidence interval: 1.51–6.30; P = 0.002) of developing severe hyperparathyroidism than whites. Conclusion This study highlighted the existence of racial differences in the circulating markers of mineral bone disorders in an African CKD population.

Solute clearance measurement in the assessment of dialysis adequacy among African continuous ambulatory peritoneal dialysis patients

Solute clearance measurement is an objective means of quantifying the dose of peritoneal dialysis (PD). Despite continued debate on the interpretation and precise prognostic value of small solute clearance in PD patients, guidelines based on solute clearance values are common in clinical practice. There is limited information on the solute clearance indices and PD adequacy parameters among this predominantly low socioeconomic status PD population. We investigated the solute clearance among continuous ambulatory peritoneal dialysis (CAPD) patients at the Charlotte Maxeke Johannesburg Academic Hospital and its relationship with other parameters of PD adequacy. Seventy patients on CAPD were studied in this cross-sectional study. Solute clearance was assessed using urea clearance (Kt/V). Linear regression analysis was used to determine factors associated with solute clearance, while analysis of variance was used to test the influence of weekly Kt/V on blood pressure (BP), hemoglobin (Hb) and other biochemical parameters. The mean age of the study population was 37.9 ± 12.4 years, 43% were females and 86% were black Africans. The mean duration on CAPD was 19.7 ± 20.8 months. Mean systolic and diastolic BP were 144 ± 28 and 92 ± 17 mm Hg, respectively. The mean Hb was 11.1 ± 2.2 g/dL and the mean weekly Kt/V was 1.7 ± 0.3. Factors like systolic BP, Hb level, serum levels of cholesterol, calcium, phosphate, parathyroid hormone and albumin were not significantly associated with the weekly Kt/V. We conclude that the dose of PD received by the majority of our patients in terms of the weekly Kt/V is within the recommended values and that this finding is significant considering the low socioeconomic background of our patients. There is no significant association between Kt/V and other indices of dialysis adequacy.