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A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Masters of Medicine in Paediatrics (MMed) Johannesburg, 2017 / Children with end-stage renal disease are commonly placed onto chronic peritoneal dialysis (PD) while awaiting transplant. Mechanical, infectious and metabolic complications of PD may lead to technique failure, morbidity or mortality. This study aims to describe the complications and associated risk factors in children on chronic PD. It consists of a retrospective record review of patients less than 18 years old enrolled on the chronic PD program between 1 January 2009 and 31 December 2013. Seventy one percent of the patients had one or more complications while on PD. The most common complication was peritonitis (54%) followed by catheter obstruction in 29%. Patients on automated peritoneal dialysis (APD) were significantly less likely to develop peritonitis than those on continuous ambulatory PD (OR 23.14, 95% CI 2.45 – 218.0, p = 0.002). We therefore recommend that PD patients be preferentially placed on APD. / MT2017

<I>Clinical Aim</I>:- To study the safety and efficacy of LDL apheresis in nephrotic patients and to assess the impact of applying a cholesterol "clamp" on the progression of renal disease. <I>Protocol</I>:- 20 patients all with a biopsy proven diagnosis were recruited. Patients were entered into 2 groups using the minimisation technique after scoring for GFR, age, sex, level of proteinuria and presence of concurrent immunosuppression. Group A (n=11) received LDL apheresis in addition to Simvastatin therapy. 12-20 treatments were given to clamp the cholesterol at or below 6.5mmol/l. Group B (n=9) received conventional lipid lowering drug therapy (Simvastatin) only. 1/Cr plots were used to asses progression of disease. Inulin GFR was also measured at entry and at 6 monthly intervals. 24 hour proteinuria, haematology, biochemistry and lipid measurements were made monthly. Patient follow up was for a mean of 17.75 months (SD 7.8). <I>Results</I>:- There was a significant reduction in Total and LDL cholesterol and Triglycerides from baseline values in the apheresis group, for 18 and 15 months respectively. In spite of this sustained lipid "clamp" there was no significant difference in proteinuria or 1/Cr plot. <I>Laboratory Studies </I>1) Lipid peroxidation was measured by diene conjugation. The methodology of this assay was extensively studied and modified to optimise its reproducibility and accuracy. Nephrotic patients did not exhibit LDL with a shortened lag time, but rate and extent of oxidation was affected by treatment. 2) Anti-oxidant status of patients pre and post LDL apheresis and endogenous levels of both groups were assessed. Apheresis did not adversely affect antioxidant profile. 3) The patients were phenotyped and genotyped for apoE polymorphism. There was an excess of the E4 allele compared to the general population.

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Estimation of the glomerular filtration rate (GFR), accepted as one of the earliest and most sensitive indicators of renal dysfunction, can be determined in horses using standard techniques In adult horses and foals, renal dysfunction can occur as a secondary complication to gastrointestinal disorders, dehydration, septicemia, endotoxemia and nephrotoxic drug administration. Measurement of renal function is an important feature not only in the diagnosis, but also in the prognosis and management of renal disease. Commonly used drugs such as phenylbutazone and gentamicin can be highly nephrotoxic under certain conditions. Of particular concern are those drugs, including the aminoglycoside antibiotics, that are eliminated almost exclusively by the kidney. Knowledge of a patients renal status prior to treatment would direct efforts at; 1) restoring kidney function prior to protracted therapy with potentially damaging drugs, 2) adjusting the dose of a life-saving drug based on the magnitude of dysfunction, or 3) selecting a drug that is not dependant on renal function for elimination. such as endogenous or exogenous renal creatinine clearance. Unfortunately, these techniques can be time consuming, dangerous to perform on fractious patients, require trained personnel and are subject to errors most often associated with improper or incomplete urine collection. Recently, tests using iohexol, a radiographic contrast agent, have been developed to estimate the GFR in human beings, dogs and cats with results that have been validated by traditional standards. Most testing protocols require a single bolus injection of iohexol, followed by 2 or 3 blood samples obtained over a few hours. Compared to traditional testing methods, samples are easily and rapidly obtained making the testing procedure less stressful for the patient. A simple method to measure GFR in horses that does not require urine collection, would allow veterinarians in a clinical setting the ability to determine a patient's renal status easily and safely. The objectives of this study were; 1) model the pharmacokinetic profile of iohexol in horse foals, 2) compare creatinine clearance, an accepted standard for GFR determination in patients, with iohexol clearance, and 3) develop sampling parameters and calculation methods for a practical test, based on iohexol clearance, that compares favorably with creatinine clearance in horse foals. Iohexol concentration time data were best described using a 3-compartment open model. Mean creatinine clearance (2.17 ml/min/kg) and mean iohexol clearance (2.15 ml/min/kg) showed good agreement. In addition, GFR values for all foals using either method were within published reference ranges for this species. The results of this study indicate that a single intravenous injection of iohexol at a dose of 150 mg/kg, followed by collection of 2 serum samples at 4 and 6 hours post injection can be used to estimate the GFR in healthy horse foals. Mean corrected GFR value (CLpredicted) for 10 foals in this study was 2.15 ml/min/kg. / Master of Science

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