Glomerular Function and Structure in Living Donors: Lessons from Single Nephron Studies

One third of the kidney transplants performed in the USA come from living kidney donors. The long-term outcome of healthy individuals who donate kidneys is mostly excellent, although recent studies have suggested that living donation is associated with a small absolute increase in the risk of end stage renal failure. Much of our understanding about the progression of kidney disease comes from experimental models of nephron loss. For this reason, living kidney donation has long been of great interest to renal physiologists. This review will summarize the determinants of glomerular filtration and the physiology that underlies post-donation hyperfiltration. We describe the ‘remnant kidney’ model of kidney disease and the reasons why such progressive kidney disease very rarely ensues in healthy humans following uninephrectomy. We also review some of the methods used to determine glomerular number and size and outline their associations

Microalbuminuria as Predictor of Early Glomerular Injury in Children and Adolescents with Sickle Cell Anaemia at Muhimbili National Hospital Dar es Salaam, Tanzania 2012

Microalbuminuria (MA) is the earliest marker of various diseases affecting the renal system. Its relevance in children and adolescents with sickle cell anaemia (SCA), who are known to be prone to renal complications, has not been fully explored in our setting. Several studies have shown microalbuminuria to be prevalent among SCA children. It is now used extensively as a sensitive test of preclinical glomerular damage. Microalbuminuria in the early stages of sickle cell nephro¬pathy is a hallmark of future deterioration of renal function. It is important to detect this early with routine surveillance. Intervention at this stage may prevent or at least delay the end stage renal disease. To determine the prevalence of microalbuminuria and its clinical correlates in children and adolescents with SCA attending sickle cell clinic at Muhimbili National Hospital. This was a hospital based descriptive cross-sectional study. Children and adolescents aged 3 – 18 years attending sickle cell clinic were randomly selected. Urine sample of all eligible children and adolescent with SCA was screened for microalbuminuria by special Micral urine taste strips (Cliawaived Microlalbumin 2-1 Combo, USA),with sensitivity and specificity of 96.5% and 98.3 respectively. The resting blood pressure (BP) measurements, haemoglobin level, were obtained and clinical events associated with microalbuminuria were recorded. Data were analyzed using Statistical Package for Social Science (SPSS) version 17 statistical packages. Chi-square test was used for categorical variables, and student t test for independent sample means. Binary logistic regression was used to analyze potential effect modifiers of microalbuminuria. The study group was made up of 120 subjects aged 3 to 18 years (53% females). Microalbuminuria (MA) was found in 29/120 (24%). None of the clinical characteristics (painful crisis, blood transfusion, abnormal pressure) were significantly related with MA. Haemoglobin levels were significantly lower in subjects with MA than in those without MA (5.9±1.2 vs 7.4±1.0g/dL, respectively)p=0.001 . In multivariate logistic regression model of MA both Hb level and age remain in the final model as clinical correlates of MA. Higher Hb level showed a protective effect against MA (Odds ratio=0.55) p=0.001 while subjects with MA were more likely to have older age. (Odds ratio=1.7) p=0.001 MA is common among children and adolescents with SCA and directly related to age and inversely related to the haemoglobin levels. Urinary MA measurement is a simple and non-invasive screening biomarker which may be utilized as part of routine health care in children and adolescents with SCA. Screening for microalbuminuria seems prudent after age 6 to 7 years especially in those with severe anaemia. Longitudinal studies are essential to determine the significance of childhood microalbuminuria in the development of renal diseas

Serum Creatinine: Not So Simple!

peer reviewedMeasuring serum creatinine is cheap and commonly done in daily practice. However, interpretation of serum creatinine results is not always easy. In this review, we will briefly remind the physiological limitations of serum creatinine due notably to its tubular secretion and the influence of muscular mass or protein intake on its concentration. We mainly focus on the analytical limitations of serum creatinine, insisting on important concept such as reference intervals, standardization (and IDMS traceability), analytical interferences, analytical coefficient of variation (CV), biological CV and critical difference. Because the relationship between serum creatinine and glomerular filtration rate is hyperbolic, all these CVs will impact not only the precision of serum creatinine but still more the precision of different creatinine-based equations, especially in low or normal-low creatinine levels (or high or normal-high glomerular filtration rate range)

The magnitude of nephron number reduction mediates intrauterine growth-restriction-induced long term chronic renal disease in the rat. A comparative study in two experimental models.

Intrauterine growth restriction (IUGR) is a risk factor for hypertension (HT) and chronic renal disease (CRD). A reduction in the nephron number is proposed to be the underlying mechanism; however, the mechanism is debated. The aim of this study was to demonstrate that IUGR-induced HT and CRD are linked to the magnitude of nephron number reduction, independently on its cause. Systolic blood pressure (SBP), glomerular filtration rate (GFR), proteinuria, nephron number, and glomerular sclerosis were compared between IUGR offspring prenatally exposed to a maternal low-protein diet (9% casein; LPD offspring) or maternal administration of betamethasone (from E17 to E19; BET offspring) and offspring with a normal birth weight (NBW offspring). Both prenatal interventions led to IUGR and a similar reduction in birth weight. In comparison to NBW offspring, BET offspring had a severe nephron deficit (-50% in males and -40% in females, p < 0.01), an impaired GFR (-33%, p < 0.05), and HT (SBP+ 17 mmHg, p < 0.05). Glomerular sclerosis was more than twofold higher in BET offspring than in NBW offspring (p < 0.05). Long-term SBP, GFR, and glomerular sclerosis were unchanged in LPD offspring while the nephron number was moderately reduced only in males (-28% vs. NBW offspring, p < 0.05). In this study, the magnitude of nephron number reduction influences long term renal disease in IUGR offspring: a moderate nephron number is an insufficient factor. Extremely long-term follow-up of adults prenatally exposed to glucocorticoids are required

A Compendium of Urinary Biomarkers Indicative of Glomerular Podocytopathy

It is well known that glomerular podocyte injury and loss are present in numerous nephropathies and that the pathophysiologic consecution of disease hinges upon the fate of the podocyte. While multiple factors play a hand in glomerulopathy progression, basic logic lends that if one monitors the podocyte's status, that may reflect the status of disease. Recent investigations have focused on what one can elucidate from the noninvasive collection of urine, and have proven that certain, specific biomarkers of podocytes can be readily identified via varying techniques. This paper has brought together all described urinary biomarkers of podocyte injury and is made to provide a concise summary of their utility and testing in laboratory and clinical theatres. While promising in the potential that they hold as tools for clinicians and investigators, the described biomarkers require further comprehensive vetting in the form of larger clinical trials and studies that would give their value true weight. These urinary biomarkers are put forth as novel indicators of glomerular disease presence, disease progression, and therapeutic efficacy that in some cases may be more advantageous than the established parameters/measures currently used in practice

Current Management of Patients With Acquired Solitary Kidney.

Persons with acquired solitary kidney, including those who have had a unilateral nephrectomy for living kidney donation, renal malignancies, or trauma, have decreased renal mass that leads to increased intraglomerular pressure and glomerular hyperfiltration. These physiologic adaptations of solitary kidney may exacerbate other preexisting and genetic conditions that could create a predisposition to or worsen glomerular pathologies, leading to unfavorable renal outcomes. Hence, these persons may benefit from special care and lifestyle modifications, including nutritional interventions. There is a lack of consensus and evidence for proper surveillance and management after nephrectomy, and misconceptions in both directions of having a "normal" versus "abnormal" kidney status may cause confusion among patients and healthcare providers pertaining to long-term kidney health monitoring and management. We have reviewed available data on the impact of lifestyle modifications, particularly nutritional measures, and pharmacologic interventions, on short- and long-term outcomes after nephrectomy. We recommend avoidance of excessively high dietary protein intake (>1 g/kg per day) and high dietary sodium intake (>4 grams/d), adequate dietary fiber intake from plant-based foods, a target body mass index of <30 kg/m2 (in non-athletes and non-bodybuilders), and judicious management of risk factors of progressive chronic kidney disease (CKD), and future studies should help to better determine optimal care practices for these persons

An easy to calculate equation to estimate GFR based on inulin clearance

Background. For the estimation of renal function on the basis of serum creatinine, either the Cockcroft-Gault (CG) equation or the MDRD formula is commonly used. Compared to MDRD (using power functions), CG has the advantage of easy calculability at the bedside. MDRD, however, approaches glomerular filtration rate (GFR) more precisely than CG and gives values corrected for a body surface area (BSA) of 1.73 m2. We wondered whether CG could be adapted to estimate GFR rather than creatinine clearance without losing the advantage of easy calculability. In this prospective study, inulin clearance under well-defined conditions was taken as the gold standard for GFR. Methods. In 182 living kidney donors, inulin clearance was measured under standardized conditions (protein, salt and water intake, overnight stay) before and after nephrectomy. Together with the serum creatinine level, and demographic and clinical data, 281 measurements of inulin clearance were used to compare the accuracy of different estimation equations. Using stepwise multiple regression, a new set of constants was defined for a CG-like equation in order to estimate GFR. Results. The MDRD equation underestimated GFR by 9%, and the quadratic equation suggested by Rule overestimated GFR by 12.4%. The new CG-like equation, even when calculated with ‘mental arithmetic-friendly' rounded parameters, showed significantly less bias (1.2%). The adapted equation is Conclusions. We propose the CG-like equation called IB-eGFR (Inulinclearance Based eGFR) to estimate GFR more reliably than MDRD, Rule's equation or the original Cockcroft-Gault equation. As our data represent a Caucasian population, the adapted equation is still to be validated for patients of other ethnicit