Association of Continuous-Equivalent Urea Clearances with Death Risk in Intermittent Hemodialysis

Background. Several reports describe favorable results from frequent hemodialysis, but due to the lack of unequivocal dose measures it is not clear whether the benefits are due to more efficient toxin removal or other factors. Methods. The associations with death risk of six continuous-equivalent urea clearance measures were compared in 57 conventional in-center hemodialysis treatment periods of 51 patients, together 114 patient years. The double pool dose measures were calculated with the Solute-Solver program and separately scaled to urea distribution volume or normalized with body surface area. Results. Mortality associated significantly with equivalent renal urea clearance (EKR) scaled to urea distribution volume (V) (p=0.033) and with EKR normalized with body surface area (BSA) (p=0.044) but not with V-scaled (p=0.059) nor BSA-normalized (p=0.183) standard clearance (stdK). Women had significantly higher normalized protein catabolic rate (nPCR), EKR/V, and stdK/V than men but slightly lower BSA-normalized dose measures and lower mortality. Protein catabolic rate and dialysis dose correlated positively with each other and with survival. Conclusions. The prognostically most valid continuous-equivalent clearance in the present material was EKR/V, calculated from double pool urea generation rate, distribution volume, and time-averaged concentration.

Risk Factors for Peritonitis in a Pediatric Dialysis Program in Guatemala, 2011–2014

Background. Peritonitis is the most common complication of peritoneal dialysis but there is limited data regarding peritonitis related risk factors in developing countries. Objective. Describe the PD program at Foundation for Children with Kidney Disease (FUNDANIER), in Guatemala, and identify peritonitis related risk factors in these patients. Methods. This retrospective open cohort study included medical records from FUNDANIER during 2011 to 2014. Baseline demographics, treatment modalities, caregivers’ characteristics, and socioeconomic status were recorded. Results. Eighty-nine medical records were included with a treatment time of 1855 months. Median age of patients was 11.3 years (range 6–17). Median duration of PD therapy was 20.8 months (range 1–28). Sixty-eight peritonitis episodes were registered; forty-eight patients (54%) remained peritonitis-free. Median time to first peritonitis episode was 5 months (range 2–16). Peritonitis rate was one episode every 27 months or 0.44 episodes per patient-year. Peritonitis rate in patients with fair housing was 2.5 times higher than in those with good housing (CI = 1.0–5.2, p=0.01). Conclusion. Housing conditions are a relevant risk factor related to peritonitis. Strategies toward preventing peritonitis must consider housing status, establishing adequate follow-up in high-risk patients. Close monitoring of technique serves to overcome understaffing issues in this setting.

Predictors of a Rapid Decline of Renal Function in Patients with Chronic Kidney Disease Referred to a Nephrology Outpatient Clinic: A Longitudinal Study

Background. Predicting the progression of kidney failure in patients with chronic kidney disease is difficult. The aim of this study was to assess the predictors of rapid kidney decline in a cohort of patients referred to a single outpatient nephrology clinic. Design. Longitudinal, prospective cohort study with a median follow-up of 3.39 years. Methods. Data were obtained from 306 patients with chronic renal failure based on serum creatinine-estimated glomerular filtration rate (eGFRcreat) < 90 mL/min/1.73 m2. After excluding patients who died (n=30) and those who developed end-stage renal failure (n=6), 270 patients were included. This population was grouped according to the rate of kidney function decline. Rapid kidney function decline was defined as an annual eGFRcreat loss > 4 mL/min/1.73 m2. We recorded nonfatal cardiovascular events at baseline and during follow-up in addition to biochemical parameters. Results. The mean loss in renal function was 1.22 mL/min/1.73 m2 per year. The mean age was 75 ± 8.8 years old, and the mean baseline eGFRcreat was 42 ± 14 mL/min/1.73 m2. Almost one-fourth of the sample (23.3% [63 patients]) suffered a rapid decline in renal function. In a logistic regression model with rapid decline as the outcome, baseline characteristics, lower serum albumin (OR: 0.313, 95% CI: 0.114–0.859), previous cardiovascular disease (OR: 1.903 95% CI: 1.028–3.523), and higher proteinuria (g/24 h) (OR: 1.817 CI 95%: 1.213–2.723) were the main predictors of rapid kidney decline. On multivariate analysis, including baseline and follow-up data, we obtained similar adjusted associations of rapid kidney decline with baseline serum albumin and proteinuria. The follow-up time was also shorter in the group with rapid rates of decline in renal function. Conclusion. Renal function remained stable in the majority of our population. Previous cardiovascular disease and cardiovascular incidents, lower serum albumin, and higher proteinuria at baseline were the main predictors of rapid kidney decline in our population.

Planar Cell Polarity Pathway in Kidney Development and Function

The evolutionarily conserved planar cell polarity (PCP) signaling pathway controls tissue polarity within the plane orthogonal to the apical-basal axis. PCP was originally discovered in Drosophila melanogaster where it is required for the establishment of a uniform pattern of cell structures and appendages. In vertebrates, including mammals, the PCP pathway has been adapted to control various morphogenetic processes that are critical for tissue and organ development. These include convergent extension (crucial for neural tube closure and cochlear duct development) and oriented cell division (needed for tubular elongation), ciliary tilting that enables directional fluid flow, and other processes. Recently, strong evidence has emerged to implicate the PCP pathway in vertebrate kidney development. In this review, we will describe the experimental data revealing the role of PCP signaling in nephrogenesis and kidney disease.

Deleterious Effects of Increased Intra-Abdominal Pressure on Kidney Function

Elevated intra-abdominal pressure (IAP) occurs in many clinical settings, including sepsis, severe acute pancreatitis, acute decompensated heart failure, hepatorenal syndrome, resuscitation with large volume, mechanical ventilation with high intrathoracic pressure, major burns, and acidosis. Although increased IAP affects several vital organs, the kidney is very susceptible to the adverse effects of elevated IAP. Kidney dysfunction is among the earliest physiological consequences of increased IAP. In the last two decades, laparoscopic surgery is rapidly replacing the open approach in many areas of surgery. Although it is superior at many aspects, laparoscopic surgery involves elevation of IAP, due to abdominal insufflation with carbonic dioxide (pneumoperitoneum). The latter has been shown to cause several deleterious effects where the most recognized one is impairment of kidney function as expressed by oliguria and reduced glomerular filtration rate (GFR) and renal blood flow (RBF). Despite much research in this field, the systemic physiologic consequences of elevated IAP of various etiologies and the mechanisms underlying its adverse effects on kidney excretory function and renal hemodynamics are not fully understood. The current review summarizes the reported adverse renal effects of increased IAP in edematous clinical settings and during laparoscopic surgery. In addition, it provides new insights into potential mechanisms underlying this phenomenon and therapeutic approaches to encounter renal complications of elevated IAP.

Moderately Decreased Dietary Salt Intake Suppresses the Progression of Renal Insufficiency in Rats with 5/6 Nephrectomy

Aim. Up to now, an appropriate salt intake in renal insufficiency has not been clearly determined. We hypothesize that even a moderate decrease in salt intake may affect functional and morphologic response of the rat remnant kidney after 5/6 nephrectomy. Methods. Subtotal nephrectomy was performed in 77 inbred 12 week-old-female AVN Wistar rats. The two groups of rats were fed either a standard or a low salt diet. Median of salt intake was 14.6 and 10.4 mg/100 g/24 h in the two groups. Results. Ten weeks after ablation, the remnant kidney parenchyma wet weight was 0.66 ± 0.16 g/100 g of body weight and 0.56 ± 0.11 g/100 g of body weight (P<0.01) in rats with a standard and low salt diet, respectively. In these two groups, systolic blood pressure was 151 ± 29 versus 126 ± 21 mmHg (P<0.05), serum creatinine levels were 164 ± 84 versus 106 ± 29 µmol/L (P<0.001), proteinuria was 84 ± 37 versus 83 ± 40 mg/100 g/24 h (N.S.), and the glomerular injury score was 2.06 ± 0.49 versus 1.43 ± 0.62 (P<0.01), respectively. Conclusion. Moderately decreased salt intake slowed down the development of ablation nephropathy in AVN inbred strain of rats.

Magnesium and Muscle Cramps in End Stage Renal Disease Patients on Chronic Hemodialysis

We evaluated the frequency and severity of muscle cramps, and the effect of dialysate magnesium on muscle cramps in 62 stable ESRD patients on chronic hemodialysis. Each subject was surveyed twice within a 6-month period. A single nephrology fellow conducted all in-person surveys. During the first survey, the patients were dialyzed with dialysate magnesium of 0.75 meq/L (0.375 mmol/L). Prior to the second survey, the dialysate magnesium was increased to 1.0 meq/L (0.50 mmol/L). The severity of cramps was scored on a 1–10 scale, with 10 indicating maximal severity. The number of patients with muscle cramps was significantly lower with dialysate magnesium of 1.0 meq/L (0.50 mmol/L) (56% versus 77%, P=0.02). No significant difference was observed in interdialytic weight gain, intradialytic ultrafiltration, dry weight, or intradialytic hypotension. The mean ± SD severity score of muscle cramps decreased from 5.34±3.61 to 3.89±3.94 (P=0.003). Seven of 31 (23%) patients in the group with low dialysate magnesium while 0/20 (0%) patients receiving high magnesium dialysate terminated hemodialysis early due to cramps (P=0.02). Both the number of patients reporting muscle cramps and the severity score decreased with higher dialysate magnesium which contributed to better adherence to hemodialysis treatments.

Peritoneal Membrane Injury and Peritoneal Dialysis

For patients with chronic renal failure, peritoneal dialysis (PD) is a common, life sustaining form of renal replacement therapy that is used worldwide. Exposure to nonbiocompatible dialysate, inflammation, and uremia induces longitudinal changes in the peritoneal membrane. Application of molecular biology techniques has led to advances in our understanding of the mechanism of injury of the peritoneal membrane. This understanding will allow for the development of strategies to preserve the peritoneal membrane structure and function. This may decrease the occurrence of PD technique failure and improve patient outcomes of morbidity and mortality.

Incremental Hemodialysis Schedule in Patients with Higher Residual Renal Function at the Start of Dialysis

We present an observational study to evaluate a progressive schedule of dose of dialysis, starting with 2 HD/week, when the renal clearance of urea was equal to or greater than 2,5 mL/min/1,73 m2 and the patient is in a stable clinical situation. From 2006 to 2011, 182 patients started hemodialysis in our center, of which 134 were included in the study. Residual renal function (RRF), Kt/V, eKru, nPCR, hemoglobin, weekly erythropoietin dose, and beta-2-microglobulin were determined at 6, 12, 18, 24, and 30 months after dialysis initiation. Seventy patients (52%) began with the progressive schedule of 2 HD/week and 64 (48%) patients began with the conventional thrice-weekly schedule (3 HD/week). The decline of RRF was lower in the group of 2 HD/week: 0,20 (0,02–0,53) versus 0,50 (0,14–1,08) mL/min/month (median and interquartile range, P=0,009). No relationship was found between the decline rate and the basal RRF. Survival analysis did not show differences between both groups. Our experience demonstrates that patients with higher residual renal function may require less than conventional 3 HD sessions per week at the start of dialysis. Twice-weekly hemodialysis schedule is safe and cost-effective and may have additional benefit in maintaining the residual renal function.

The Choice of the Iodinated Radiographic Contrast Media to Prevent Contrast-Induced Nephropathy

In patients with preexisting renal impairment, particularly those who are diabetic, the iodinated radiographic contrast media may cause contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI), that is, an acute renal failure (ARF), usually nonoliguric and asymptomatic, occurring 24 to 72 hours after their intravascular injection in the absence of an alternative aetiology. Radiographic contrast media have different osmolalities and viscosities. They have also a different nephrotoxicity. In order to prevent CIN, the least nephrotoxic contrast media should be chosen, at the lowest dosage possible. Other prevention measures should include discontinuation of potentially nephrotoxic drugs, adequate hydration with i.v. infusion of either normal saline or bicarbonate solution, and eventually use of antioxidants, such as N-acetylcysteine, and statins.