Body Mass Index and Glomerular Hyperfiltration in Renal Transplant Recipients: Cross-Sectional Analysis and Long-Term Impact

Obesity is a risk factor for renal graft loss. Higher body mass index (BMI) in native kidneys is associated with glomerular hyperfiltration. Whether higher BMI in renal transplants is associated with hyperfiltration is unknown. We investigated the impact of BMI on renal hemodynamics 1 year post-transplant. We analyzed glomerular filtration rate (GFR, (125)I-iothalamate) and effective renal plasma flow (ERPF, (131)I-hippurate) in 838 kidney transplants. Data were analyzed for all patients and for the subpopulation without diabetes. Long-term impact of BMI and renal hemodynamics were explored by Cox-regression. With higher BMI GFR and filtration fraction (FF) increased significantly. Multivariate analysis supported impact of BMI on GFR (adjusted r(2) of the model 0.275) and FF (adjusted r(2) of the model 0.158). This association was not explained by diabetes mellitus. On Cox-regression analysis, lower GFR and higher FF were independent determinants of overall graft loss and graft loss by patient mortality. Lower GFR and higher BMI were determinants of death-censored graft loss, with borderline contribution of higher FF. In renal transplants higher BMI is independently associated with higher GFR and FF one year posttransplant, suggesting glomerular hyperfiltration with altered afferent-efferent balance. Mechanisms underlying the long-term prognostic impact of hyperfiltration deserve further exploration.     

Reduction of protein intake decreases glomerular filtration rate in young Type 1 (insulin-dependent) diabetic patients mainly in hyperfiltering patients

Summary The influence of different protein intake on renal function was studied in 16 Type 1 (insulin-dependent) diabetic patients, aged 15–23 years, with onset of diabetes before puberty and with a duration of diabetes between 5 and 20 years. The glomerular filtration rate, renal plasma flow, albumin excretion rate, and blood pressure were examined in a cross-over randomised order after 10 days on isocaloric diets with either 10% (i.e. 0.9±0.06 g·kg^–1·day^–1) or 20% (1.9±0.1 g·kg^–1·day^–1) of the calories as protein, the latter being equal to the recommended diet. Dietary compliance was evaluated using fractional phosphate excretion and overnight urea excretion. Glomerular filtration rate was lower after the low-protein diet compared to the usual protein diet (p<0.001). Patients with glomerular filtration rate above +2 SD of the normal mean on the usual protein diet (n=6) exhibited the steepest fall in glomerular filtration rate with a mean decrease of 20ml/min compared to 7 ml/min in those with initially normal glomerular filtration (p=0.01). Filtration fraction tended to decrease on low protein diet, more so in initially hyperfiltering patients (p=0.09). Renal plasma flow remained unchanged. In patients with elevated glomerular filtration rate on usual protein diet, albumin excretion rate and systolic, but not diastolic blood pressure, were decreased on low protein diet (p=0.03 and p=0.01, respectively) but not in initially normal-filtering patients. Mean blood glucose and serum fructosamine were unchanged on both diets. In conclusion, low protein diet decreases glomerular filtration rate independently of glycaemic control in young Type 1 diabetic patients and more so in hyperfiltering patients. This decline in glomerular filtration rate is accompanied by a decrease in albumin excretion rate and systolic blood pressure in hyper-filtering patients.     

The Association between Glomerular Hyperfiltration and Left Ventricular Structure and Function in Patients with Primary Aldosteronism

Background: Glomerular hyperfiltration has been recently noticed as an important issue in primary aldosteronism (PA) patients. However, its effect on the cardiovascular system remains unknown.Methods: We prospectively analyzed 47 PA patients including 11 PA patients with estimated glomerular filtration rate (eGFR) > 130 ml/min per 1.73 m² (group 1), and 36 PA patients with eGFR 90-110 ml/min per 1.73 m² (group 2). Fourteen essential hypertension (EH) patients with eGFR 90-110 ml/min per 1.73 m² were included as the control group (group 3). Echocardiography including left ventricular mass index (LVMI) measurement and tissue Doppler imaging (TDI) was performed. Predicted left ventricular mass (LVM) was calculated. Inappropriate LVM was defined as an excess of > 35% from the predicted value.Results: The value of LVMI decreased significantly in order from groups 1 to 3 (group 1>2>3). While group 2 had a significantly higher percentage of inappropriate LVM than group 3, the percentage of inappropriate LVM were comparable in groups 1 and 2. Group 1 had a higher mitral E velocity, E/A ratio than that of group 2. In the TDI study, the E/E'' ratio also decreased significantly in order from groups 1 to 3 (group 1>2>3). Group 2 had lower E'' than that of group 3, although the E'' of group 1 and 2 were comparable.Conclusions: Although PA patients with glomerular hyperfiltration were associated with higher LVMI, higher mitral E velocity, higher E/E'' ratio, they had comparable E'' with PA patients with normal GFR. This phenomenon may be explained by higher intravascular volume in this patient group.     

Renal Hyperfiltration in Prediabetes Confirmed by Fasting Plasma Glucose and Hemoglobin A1c

Background: The aim of the study was to confirm that glomerular hyperfiltration, an early and reversible stage of kidney damage, is associated in patients with prediabetes and prehypertension. Methods: In total, 5003 people aged between 35 and 69 years who had participated in the Shizuoka part of the Japan Multi-Institutional Collaborative Cohort (J-MICC) study took part in the study. Prevalence of hyperfiltration [the estimated glomerular filtration rate (eGFR) above the age- /sex-specific 95th percentile] was compared among different stages of prediabetes [fasting plasma glucose (FPG) < 100, 100–109, 110–125, and ≥126 mg/dL; and/or hemoglobin A1c (HbA1c) < 5.7, 5.7–6.0, 6.1–6.4 and ≥6.5% for no prediabetes, stage 1 prediabetes, stage 2 prediabetes, and overt diabetes, respectively] and prehypertension (blood pressure <120/80, 120–129/80–84, 130–139/85–89, and ≥140/90 mmHg for no prehypertension, stage 1 prehypertension, stage 2 prehypertension, and overt hypertension, respectively). Results: The prevalence of hyperfiltration increased with increasing stages of prediabetes (odds ratios: 1.25, 1.68, and 2.37 using FPG, and 1.26, 2.15, and 2.45 using HbA1c for stage 1 prediabetes, stage 2 prediabetes, and diabetes, respectively, relative to no prediabetes). Prehypertension, however, was not associated with hyperfiltration. Conclusion: The results confirmed that the prevalence of glomerular hyperfiltration increased with increasing stages (i.e., worsening) of prediabetes. Because both FPG and HbA1c showed similar association with hyperfiltration, either of these can be used to identify subjects who are at increased risk of nephropathy. Therefore, the functioning of kidneys should be monitored in subjects with prediabetes. Prompt treatment of hyperglycemia is necessary in subjects with hyperfiltration to prevent it to cause nephropathy.     

Early inhibition of the renin‐angiotensin system improves the long‐term graft survival of single pediatric donor kidneys transplanted in adult recipients

Transplanting single pediatric donor kidneys into adult recipients has an increased risk of hyperfiltration injury and graft loss. It is unknown if renin‐angiotensin system (RAS) blockers are beneficial in this setting. We retrospectively analyzed 94 adults who received single kidneys from donors <10 years old during 1996–2009. The recipients were divided into group 1 with RAS blockers (n = 40) and group 2 without RAS blockers (n = 54) in the first year of transplant. There was no significant difference in any donor/recipient demographic between the two groups. Graft function, incidence of delayed graft function, acute rejection, and persistent proteinuria were not statistically different either. Kaplan–Meier estimated death‐censored graft survivals were significantly better in group 1 than in group 2: 95 vs. 81.2%, 82.4 vs. 61.2%, 72.6 vs. 58.5%, and 68.5 vs. 47.2% at 1, 3, 5, and 7 years, respectively (log rank P = 0.043). Multivariable analysis found persistent proteinuria was a risk factor for graft loss (OR 2.70, 95% CI 1.33–5.49, P = 0.006), while RAS blockers reduced the risk of graft loss (OR 0.38, 95% CI 0.18–0.79, P = 0.009). Early RAS blockade therapy in the first year of transplant is associated with superior long‐term graft survival among adults transplanted with single pediatric donor kidneys.     

Glomerular hyperfiltration in type 1 diabetes mellitus results from primary changes in proximal tubular sodium handling without changes in volume expansion

BACKGROUND: Glomerular hyperfiltration plays a role in the pathophysiology of diabetic nephropathy. An increase in the glomerular filtration rate (GFR) could result from primary actions at the glomerular/vascular level or could be the consequence of a primary increase in proximal tubular sodium reabsorption resulting in systemic volume expansion. Recently it was hypothesized that an increase in sodium reabsorption may lead to glomerular hyperfiltration through the tubulo-glomerular feedback mechanism (tubular-hypothesis) without volume expansion. DESIGN: We have studied 54 normoalbuminuric patients with type 1 diabetes. The GFR was measured by inulin clearance. Proximal and distal sodium reabsorption were calculated according to standard formulas using the free water clearance technique. Plasma volume, measured by the (125)I-albumin method, atrial natriuretic peptide (ANP) and the second messenger cyclic guanosine-3,5-monophosphate (c-GMP) were used as markers of extracellular volume expansion. RESULTS: Glomerular hyperfiltration (GFR >or= 130 mL min(-1) 1.73 m(-2)) was present in 14 out of 55 patients with diabetes (25%). There were no differences in plasma volume between normo-(NF) and hyper-filtrating (HF) patients (2933 +/- 423 in NF vs. 3026 +/- 562 mL in HF, NS). Also plasma ANP and c-GMP levels were not significantly different between the groups. The fractional proximal reabsorption of sodium was significantly increased in HF [fPRNa(+) (%) 90.1 +/- 2.0 vs. 91.5 +/- 1.6, P = 0.02]. There were no differences in distal sodium reabsorption or distal sodium load (approximately macula densa concentration of NaCl) in both groups. CONCLUSIONS: Our data suggest that the primary event in diabetic glomerular hyperfiltration is an increase in proximal tubular sodium reabsorption. They do not support the hypothesis that systemic volume expansion or ANP mediate glomerular hyperfiltration in patients with normoalbuminuric type 1 diabetes. As such, changes in tubular sodium handling most probably influence tubulo-glomerular feedback.