Renal Negative Pressure Treatment as a Novel Therapy for Heart Failure Induced Renal Dysfunction

Congestion is the primary pathophysiologic lesion in most heart failure (HF) hospitalizations. Renal congestion increases renal tubular pressure, reducing glomerular filtration rate (GFR) and diuresis. Because each nephron is a fluid filled column, renal negative pressure therapy (rNPT) applied to the urinary collecting system should reduce tubular pressure, potentially improving kidney function. We evaluated the renal response to rNPT in congestive HF. Ten anesthetized ∼80 kg pigs underwent instrumentation with bilateral renal pelvic JuxtaFlow® catheters. GFR was determined by iothalamate clearance (mGFR) and renal plasma flow (RPF) by para-aminohippurate clearance. Each animal served as its own control with randomization of L vs. R kidney to -30mmHg rNPT or no rNPT mGFR and RPF were measured simultaneously from the rNPT and no rNPT kidney. Congestive HF was induced via cardiac tamponade maintaining central venous pressure at 20-22.5mmHg throughout the experiment. Prior to HF induction, rNPT increased natriuresis, diuresis, and mGFR compared with the control kidney (p<0.001 for all). Natriuresis, diuresis, and mGFR, decreased following HF (p<0.001 for all) but were higher in rNPT kidney vs. control (p<0.001 for all). RPF decreased during HF (p<0.001) without significant differences between rNPT treatments. During HF the rNPT kidney had similar diuresis and natriuresis (p>0.5 for both), and higher fractional excretion of sodium (p=0.001) compared with the non-rNPT kidney in the no-HF period. In conclusion, rNPT resulted in significantly increased diuresis, natriuresis, and mGFR, with or without experimental HF. rNPT improved key renal parameters of the congested cardio-renal phenotype.

Early Glomerular Hyperfiltration and Long-Term Kidney Outcomes in Type 1 Diabetes

Background and objectivesGlomerular hyperfiltration has been considered to be a contributing factor to the development of diabetic kidney disease (DKD). To address this issue, we analyzed GFR follow-up data on participants with type 1 diabetes undergoing 125I-iothalamate clearance on entry into the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications study.Design, setting, participants, & measurementsThis was a cohort study of DCCT participants with type 1 diabetes who underwent an 125I-iothalamate clearance (iGFR) at DCCT baseline. Presence of hyperfiltration was defined as iGFR levels ≥140 ml/min per 1.73 m2, with secondary thresholds of 130 or 150 ml/min per 1.73 m2. Cox proportional hazards models assessed the association between the baseline hyperfiltration status and the subsequent risk of reaching an eGFR <60 ml/min per 1.73 m2.ResultsOf the 446 participants, 106 (24%) had hyperfiltration (iGFR levels ≥140 ml/min per 1.73 m2) at baseline. Over a median follow-up of 28 (interquartile range, 23, 33) years, 53 developed an eGFR <60 ml/min per 1.73 m2. The cumulative incidence of eGFR <60 ml/min per 1.73 m2 at 28 years of follow-up was 11.0% among participants with hyperfiltration at baseline, compared with 12.8% among participants with baseline GFR <140 ml/min per 1.73 m2. Hyperfiltration was not significantly associated with subsequent risk of developing an eGFR <60 ml/min per 1.73 m2 in an unadjusted Cox proportional hazards model (hazard ratio, 0.83; 95% confidence interval, 0.43 to 1.62) nor in an adjusted model (hazard ratio, 0.77; 95% confidence interval, 0.38 to 1.54). Application of alternate thresholds to define hyperfiltration (130 or 150 ml/min per 1.73 m2) showed similar findings.ConclusionsEarly hyperfiltration in patients with type 1 diabetes was not associated with a higher long-term risk of decreased GFR. Although glomerular hypertension may be a mechanism of kidney injury in DKD, higher total GFR does not appear to be a risk factor for advanced DKD.

Overweight young female kidney donors have low renal functional reserve postdonation

Maintenance of adequate renal function after living kidney donation is important for donor outcome. Overweight donors, in particular, may have an increased risk for end-stage kidney disease (ESKD), and young female donors have an increased preeclampsia risk. Both of these risks may be associated with low postdonation renal functional reserve (RFR). Because we previously found that higher body mass index (BMI) was associated with lower postdonation RFR, we now studied the relationship between BMI and RFR in young female donors. RFR, the rise in glomerular filtration rate (GFR) (125I-iothalamate clearance) during dopamine, was measured in female donors (<45 yr) before and after kidney donation. Donors who are overweight (BMI >25) and nonoverweight donors were compared by Studentʼs t-test; the association was subsequently explored with regression analysis. We included 105 female donors [age 41 (36–44) median(IQR)] with a BMI of 25 (22–27) kg/m2. Predonation GFR was 118 (17) ml/min [mean(SD)] rising to 128 (19) ml/min during dopamine; mean RFR was 10 (10) ml/min. Postdonation GFR was 76 (13) ml/min, rising to 80 (12); RFR was 4 (6) ml/min ( P < 0.001 vs. predonation). In overweight donors, RFR was fully lost after donation (1 ml/min vs. 10 ml/min predonation, P < 0.001), and BMI was inversely associated with RFR after donation, independent of confounders (standardized β 0.37, P = 0.02). Reduced RFR might associate with the risk of preeclampsia and ESKD in kidney donors. Prospective studies should explore whether RFR is related to preeclampsia and whether BMI reduction before conception is of benefit to overweight female kidney donors during and after pregnancy.