Progression of kidney damage in Balkan endemic nephropathy: a 15-year follow-up of patients with kidney biopsy examination

Progression of kidney damage was studied in 18 patients with Balkan endemic nephropathy (BEN), with a mean 15-year follow-up after renal biopsy. According to kidney function, estimated by 99mTc-DTPA clearance, patients were divided into three groups: with apparently normal kidney function (clearance 103.5+/-21.3 mL/min/1.73 m2), with incipient renal failure (clearance 65.5 +/- 11.3), and with advanced renal failure (clearance 28.0+/-6.2). The mean yearly decrease of glomerular filtration rate was 2.74 mL/min. In two patients, an increase of kidney function was recorded. Six patients become dialysis dependent, two from the group with incipient renal failure, but all four from the group with advanced renal failure. Three patients died after 8 to 12 years of follow-up, one from causes unrelated to kidney disease and two from end-stage renal failure. This study has shown that BEN is characterized by a slow course and prolonged evolution, modified by medical supervision and treatment.     

Kidney transplantation from donors with rhabdomyolysis and acute renal failure

Rhabdomyolysis in deceased donors usually causes acute renal failure (ARF), which may be considered a contraindication for kidney transplantation. From January 2012 to December 2016, 30 kidneys from 15 deceased donors with severe rhabdomyolysis and ARF were accepted for transplantation at our center. The peak serum creatinine (SCr) kinase, myoglobin, and SCr of the these donors were 15 569±8597 U/L, 37 092±42 100 μg/L, and 422±167 μmol/L, respectively. Two donors received continuous renal replacement therapy due to anuria. Six kidneys exhibited a discolored appearance (from brown to glossy black) due to myoglobin casts. The kidney transplant results from the donors with rhabdomyolysis donors were compared with those of 90 renal grafts from standard criteria donors (SCD). The estimated glomerular filtration rate at 2 years was similar between kidney transplants from donors with rhabdomyolysis and SCD (70.3±14.6 mL/min/1.73 m² vs 72.3±15.1 mL/min/1.73 m²). We conclude that excellent graft function can be achieved from kidneys donors with ARF caused by rhabdomyolysis.     

Safe Conversion From Tacrolimus to Belatacept in High Immunologic Risk Kidney Transplant Recipients With Allograft Dysfunction

There is no literature on the use of belatacept for sensitized patients or regrafts in kidney transplantation. We present our initial experience in high immunologic risk kidney transplant recipients who were converted from tacrolimus to belatacept for presumed acute calcineurin inhibitor (CNI) toxicity and/or interstitial fibrosis/tubular atrophy. Six (mean age = 40 years) patients were switched from tacrolimus to belatacept at a median of 4 months posttransplant. Renal function improved significantly from a peak mean estimated glomerular filtration rate (eGFR) of 23.8 ± 12.9 mL/min/1.73 m² prior to the switch to an eGFR of 42 ± 12.5 mL/min/1.73 m² (p = 0.03) at a mean follow‐up of 16.5 months postconversion. No new rejection episodes were diagnosed despite a prior history of rejection in 2/6 (33%) patients. Surveillance biopsies performed in 5/6 patients did not show subclinical rejection. No development of donor‐specific antibodies (DSA) was noted. In this preliminary investigation, we report improved kidney function without a concurrent increase in risk of rejection and DSA in six sensitized patients converted from tacrolimus to belatacept. Improvement in renal function was noted even in patients with chronic allograft fibrosis without evidence of acute CNI toxicity. Further studies with protocol biopsies are needed to ensure safety and wider applicability of this approach.     

Use of peritoneal ultrafiltration in the elderly refractory congestive heart failure patients

Background

Refractory congestive heart failure (RCHF), due to its high mortality and hospitalization rates, is a growing health problem. In this study, as an alternative and/or supportive treatment to conventional medical therapies, we have evaluated the clinical value of peritoneal ultrafiltration, performed as a single daily exchange with icodextrin or conventional dextrose-based peritoneal dialysis solutions, in elderly patients with RCHF.

Methods

This was an observational study of 6 elderly patients with RCHF and non-terminal chronic kidney disease (CKD). Their mean age was 72.8?±?4.9?years. Four of the six patients had NYHA class 4 and two had NYHA class 3 RCHF and a medical history of 18.6?±?14.9?days/year hospitalization on average, due to decompensated congestive heart failure (CHF). Their baseline glomerular filtration rate, as calculated by the MDRD formula was 49.4?±?14.6?mL/min/1.73 m². During hospitalization, patients were initially treated with several sessions of continuous veno-venous hemofiltration and, following the achievement of hemodynamic stabilization, peritoneal ultrafiltration was initiated as the maintenance ultrafiltration modality. Patients were followed up monthly in terms of their clinical status, hospitalization rates, weight changes, serum sodium levels, and renal function. Echocardiographic changes were also evaluated every 3?months.

Results

All patients tolerated peritoneal ultrafiltration well, their functional status improved by 1 or 2 NYHA classes to reach a mean of NYHA class 2 CHF status. During the follow-up period, with a mean daily ultrafiltration rate of 850?±?176?mL, no hospitalization for decompensated CHF or acute renal failure was required. The patients?? renal function was well preserved, with a mean GFR of 49?±?14.6?mL/min/1.73 m² at baseline and 51.6?±?22.9?mL/min/1.73 m² at the 6th month of the study. Additionally, their mean serum sodium levels increased from 128?±?5.7?mEq/L to 138?±?5?mEq/L. Echocardiographic evaluation did not show any significant changes during the observation period. No peritonitis or other non-infectious complication of chronic peritoneal dialysis was seen in any of the patients.

Conclusions

Peritoneal ultrafiltration seems to be an efficient and safe procedure and a treatment of choice in elderly patients with RCHF without non-terminal CKD. Peritoneal ultrafiltration improves the quality of life and the effort capacity, and reduces hospitalization rates due to decompensated heart failure and acute renal failure.     

Efficacy of Follow-up Care System of Living Kidney Donors in Monitoring of Residual Kidney Function

Background

The possibility of an increased risk of end-stage renal disease is a major concern associated with living kidney donation. Therefore, monitoring of residual kidney function becomes most essential.

The Renal Safety Profile of Fluvastatin: Results of a Pooled Analysis

A pooled analysis was designed to evaluate the effects of fluvastatin on the kidney, in terms of renal adverse events, laboratory abnormalities, and renal function over time. An analysis of adverse events was performed on data from 30 completed clinical trials of fluvastatin in 11,815 patients. An analysis of renal function was also performed on data from patients who participated in long-term studies >6 months in treatment duration. Creatinine clearance was calculated using the Cockcroft-Gault formula. Mean creatinine clearance values were in the normal to near-normal range at baseline. Changes in creatinine clearance and serum creatinine from baseline were similar in fluvastatin-treated patients and placebo-treated patients. In the all-fluvastatin group, mean creatinine clearance (±standard deviation) increased from 87.8 (±42.8) mL/min at baseline to 89.4 (±41.2) mL/min at endpoint. In the placebo group, mean creatinine clearance (± standard deviation) increased from 87.7 (± 43.9) mL/min at baseline to 88.7 (±41.4) mL/min at endpoint. In the all-fluvastatin group, mean serum creatinine (± standard deviation) decreased from 1.14 (±0.20) mg/dL at baseline to 1.11 (±0.20) mg/dL at endpoint. In the placebo group, mean serum creatinine (±standard deviation) decreased from 1.15 (±0.22) mg/dL at baseline to 1.12 (±0.22) mg/dL at endpoint. The incidence of renal adverse events was low and comparable between the fluvastatin and placebo treatment groups. This pooled analysis demonstrates that fluvastatin treatment across the approved daily dose range of 20 mg to 80 mg does not adversely affect creatinine or creatinine clearance over time in dyslipidemic patients.     

Bariatric surgery and progression of chronic kidney disease

BackgroundObesity is an independent predictor for the development and progression of chronic kidney disease (CKD). The effect of weight reduction on the progression of kidney disease in patients with pre-existing CKD is unclear.MethodsWe conducted a retrospective study at a U.S. university hospital of patients with stage 3 CKD (glomerular filtration rate [GFR] 30–59 mL/min/1.73 m²) who had undergone bariatric surgery. The renal function of the included patients was recorded for a 2-year period after surgery to analyze the rate of loss or improvement in renal function. The estimated GFR was calculated using the Modification of Diet in Renal Disease 4-variable formula. Patients who developed acute renal failure in the postoperative period were excluded.ResultsA total of 25 patients with stage 3 CKD were included. Their average body mass index at surgery was 49.8 kg/m², the mean GFR was 47.9 mL/min/1.73 m², and the mean serum creatinine was 1.4 mg/dL. The body mass index had decreased to 38.4 kg/m² (paired t test, P < .001) at the end of 6 months and to 34.5 kg/m² (P < .001) at the end of 12 months. The mean systolic blood pressure had decreased from 133 ± 13 to 128 ± 17 mm Hg at the end of 12 months. The mean GFR at 6 months of follow-up had improved to 56.6 mL/min/1.73 m² (P < .001) and to 61.6 mL/min/1.73 m² (P < .001) at 12 months.ConclusionThe renal function of patients with CKD might improve after bariatric surgery. Larger and long-term studies are warranted to further analyze the effect of bariatric surgery on proteinuria and hard end-points such as the development of end-stage renal disease.     

Kidney outcomes in patients with liver cirrhosis and chronic kidney disease receiving an orthotopic liver transplant alone

Kidney transplant in patients with liver cirrhosis and nondialysis chronic kidney disease (CKD) is controversial. We report 14 liver cirrhotic patients who had persistently low MDRD‐6 estimated glomerular filtration rate (e‐GFR) <40 mL/min/1.73 m² for ≥3 months and underwent either liver transplant alone (LTA; n=9) or simultaneous liver‐kidney transplant (SLKT; n=5). Pretransplant, patients with LTA compared with SLKT had lower serum creatinine (2.5±0.73 vs 4.6±0.52 mg/dL, P=.001), higher MDRD‐6 e‐GFR (21.0±7.2 vs 10.3±2.0 mL/min/1.73 m², P=.002), higher 24‐hour urine creatinine clearance (34.2±8.8 vs 18.0±2.2 mL/min, P=.002), lower proteinuria (133.2±117.7 vs 663±268.2 mg/24 h, P=.0002), and relatively normal kidney biopsy and ultrasound findings. Post‐LTA, the e‐GFR (mL/min/1.73 m²) increased in all nine patients, with mean e‐GFR at 1 month (49.8±8.4), 3 months (49.6±8.7), 6 months (49.8±8.1), 12 months (47.6±9.2), 24 months (47.9±9.1), and 36 months (45.1±7.3) significantly higher compared to pre‐LTA e‐GFR (P≤.005 at all time points). One patient developed end‐stage renal disease 9 years post‐LTA and another patient expired 7 years post‐LTA. The low e‐GFR alone in the absence of other markers or risk factors of CKD should not be an absolute criterion for SLKT in patients with liver cirrhosis.     

Living-Donor Kidney Transplantation: Donor-Recipient Function Correlation

Background

With the rising prevalence of living-donor kidney transplantation, evaluation of factors correlated with renal function in the donor-recipient pair constitutes a main goal for kidney transplantation clinicians. Our objective was to analyze the more relevant donor characteristics that contribute to donor and recipient estimated glomerular filtration rates (eGFR) after 1 year.

Being Overweight Is Related to Faster Decline in Annual Glomerular Filtration Rate in Kidney Transplant

Few studies have examined the relationship between non-immunological factors and glomerular filtration rate (GFR) decline in kidney transplant. Correcting these factors in native kidneys slows the progression of chronic kidney disease. The aim of this study was to analyze the association between the control of non-immunological factors and the annual decline of GFR.

Higher Renal Allograft Function in Deceased-Donor Kidney Transplantation Rather Than in Living-Related Kidney Transplantation

Objectives

To compare the clinical outcome of kidney transplantation from living-related and deceased donors.

Is There Any Association Between Triglyceride–Glucose Index and Graft Function in Kidney Transplant Recipients?

BackgroundAlthough previous studies have illustrated the relationship between chronic kidney disease, coronary artery disease, erectile dysfunction, and the triglyceride–glucose index (TyGi), the relationship between this index and postoperative graft function in patients undergoing renal transplantation has yet to be investigated. In the present study, we aimed to reveal the association between the TyGi and renal graft outcomes in patients who underwent renal transplantation.MethodsWe retrospectively collected data on living and cadaveric kidney donor recipients between May 2019 and April 2022. The recipients’ age, sex, body mass index, preoperative fasting glucose and triglyceride levels, TyGi, estimated glomerular filtration rate (eGFR), and serum creatinine measurement data were recorded. The patients were divided into 2 groups according to their GFR values (group 1: GFR <60 mL/min/1.73 m²; group 2: GFR ≥60 mL/min/1.73 m²). Follow-up serum creatinine–eGFR levels and TyGi measurements were compared between the recipients in group 1 and group 2.ResultsThe mean TyGi measurements of the recipients were 8.79 ± 0.64 in group 1 and 8.83 ± 0.72 in group 2. There was no statistically significant difference in terms of the TyGi measurements between the 2 groups (P >. 05). No statistically significant correlation was found between the recipients’ creatinine, eGFR, and TyGi at 1st, 6th, and 12th postoperative months (P > .05).ConclusionsWe believe that the relationship between the TyGi and renal graft function can be more clearly understood in prospective studies that include a higher number of patients and a longer follow-up period.     

Association of Mineral Bone Disorder With Decline in Residual Kidney Function in Incident Hemodialysis Patients

Abnormalities of mineral bone disorder (MBD) parameters have been suggested to be associated with poor renal outcome in predialysis patients. However, the impact of those parameters on decline in residual kidney function (RKF) is uncertain among incident hemodialysis (HD) patients. We performed a retrospective cohort study in 13,772 patients who initiated conventional HD during 2007 to 2011 and survived 6 months of dialysis. We examined the association of baseline serum phosphorus, calcium, intact parathyroid hormone (PTH), and alkaline phosphatase (ALP) with a decline in RKF. Decline in RKF was assessed by estimated slope of renal urea clearance (KRU) over 6 months from HD initiation. Our cohort had a mean ± SD age of 62 ± 15 years; 64% were men, 57% were white, 65% had diabetes, and 51% had hypertension. The median (interquartile range [IQR]) baseline KRU level was 3.4 (2.0, 5.2) mL/min/1.73 m². The median (IQR) estimated 6-month KRU slope was −1.47 (−2.24, −0.63) mL/min/1.73 m² per 6 months. In linear regression models, higher phosphorus categories were associated with a steeper 6-month KRU slope compared with the reference category (phosphorus 4.0 to <4.5 mg/dL). Lower calcium and higher intact PTH and ALP categories were also associated with a steeper 6-month KRU slope compared with their respective reference groups (calcium 9.2 to <9.5 mg/dL; intact PTH 150 to <250 pg/mL; ALP <60 U/L). The increased number of parameter abnormalities had an additive effect on decline in RKF. Abnormalities of MBD parameters including higher phosphorus, intact PTH, ALP and lower calcium levels were independently associated with decline in RKF in incident HD patients. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.     

Structural and Functional Adaptation of the Remnant Kidney After Living Kidney Donation: Long-Term Follow-up

Objective

Several adjustments occur after nephrectomy (NT) in the donor's remnant kidney. We investigated kidney donors 10 years after NT and compared several parameters before and after transplantation.

Simultaneous Intestinal and Kidney Transplantation in Adults

Aim of the study: Intestinal transplantation (IT) is a life-saving procedure for carefully selected patients with intestinal failure. We evaluated patients who had undergone simultaneous intestinal and kidney transplantation (SIKT) to determine whether UK guidelines for inclusion of a renal allograft (dialysis dependent or estimated glomerular filtration rate ((eGFR)) < 45 ml/min/1.73 m²) are justified. Methods: A single centre analysis was undertaken of adults undergoing IT at the Cambridge Transplant Centre between December 2007 and January 2016. A prospectively maintained database was used to identify SIKT recipients and determine outcomes. Results: Over this period, 63 intestinal transplants were performed. Seven (11.1%) recipients received a SIKT. Five were pre-dialysis (median eGFR 29 ml/min/1.73 m², range 16–36 ml/min/1.73 m²). One recipient was on dialysis, and one needed bilateral nephrectomy at transplant. There were no primary kidney allograft failures and at three months, the median eGFR (55 ml/min/1.73 m² range 39–124) was similar to recipients of IT alone (median eGFR 56 ml/min/1.73 m² range 17–143 ml/min/1.73 m²). Two recipients required dialysis due to sepsis related kidney injury and died from multi-organ failure (20 and 63 months). Two died with a functioning renal transplant (10 and 15 months). The remaining three patients are alive at follow up (12–96 months) with an eGFR of 20–45 ml/min/1.73 m². Conclusion: Patients with significant renal impairment (eGFR <45 ml/min/1.73 m²), and receiving dialysis may benefit from SIKT. Patient survival and renal function are broadly comparable to those undergoing IT alone. Further studies are required to justify allocation of a kidney to this complex high risk group.     

Predictors of Left Ventricular Hypertrophy in Patients with Chronic Kidney Disease

The aim of the present study is to determine the prevalence and predictors of left ventricular hypertrophy in patients with stage 3 or 4 chronic kidney disease. Thirty-four patients were included. In addition to hematological and biochemical evaluations, echocardiography and ambulatory blood pressure monitoring were performed both at the beginning and at the end of the first year. Echocardiographic left ventricular mass was calculated and indexed to body surface area to calculate left ventricular mass index (LVMI). Left ventricular hypertrophy was diagnosed if LVMI >131 g/m² in male and >100 g/m² in female patients. During the follow-up period, estimated glomerular filtration rate decreased from 36.6±11.7 to 31.0±14.0 mL/min (p = 0.03), while LVMI increased from 130.2±35.6 to 140.5±30.5 g/m² (p = 0.055). Left ventricular hypertrophy was detected in 67.6% of the patients at the baseline and in 89.7% at the end of the study (p = 0.011). The independent predictors of the final LVMI were age (p = 0.035), baseline day-time systolic blood pressure (p = 0.01), baseline C-reactive protein (p = 0.001), and the decrease in glomerular filtration rate during the follow-up (p = 0.002). Left ventricular hypertrophy is quite frequent among patients with stage 3 or 4 chronic kidney disease, and its prevalence increases while glomerular filtration rate decreases during the follow-up. The early detection of left ventricular hypertrophy and both prevention of the deterioration of renal function and aggressive blood pressure control may help to achieve a decrease in cardiovascular morbidity and mortality in these patients.     

Long-term renal and overall survival of critically ill patients with acute renal injury who received continuous renal replacement therapy

Background: Acute kidney injury (AKI) is associated with the increased short-term mortality of critically ill patients on continuous renal replacement therapy (CRRT). The aim of this research was to evaluate the association of kidney function at discharge with the long-term renal and overall survival of critically ill patients with AKI who were on CRRT in an intensive care unit (ICU).

Methods: We retrospectively collected data for critically ill patients with AKI who were admitted to ICU on CRRT at a tertiary metropolitan hospital in China between 2008 and 2013. The patients were followed up to their death or to 30 September 2016 by telephone.

Results: A total of 403 patients were enrolled in this study. The 1-, 3- and 5-year patient survival rates were 64.3?±?2.4, 55.8?±?2.5 and 46.3?±?2.7%, respectively. In multivariate analysis, age, sepsis, decreased renal perfusion (including volume contraction, congestive heart failure, hypotension and cardiac arrest), preexisting kidney disease, Apache II score, Saps II score, vasopressors and eGFR <45?mL/min/1.73?m² at discharge were independent factors for worse long-term patient survival. And age, preexisting kidney disease, Apache II score, mechanical ventilation (MV) and eGFR <45?mL/min/1.73?m² at discharge were also associated with worse renal survival.

Conclusions: This study showed that impaired kidney function at discharge was shown to be an important risk factor affecting the long-term renal survival rates of critically ill patients with AKI. An eGFR <45?mL/min/1.73?m² was an independent risk factor for decreased overall survival and renal survival.     

Kidney Function and Risk of Cardiovascular Disease and Mortality in Kidney Transplant Recipients: The FAVORIT Trial

In kidney transplant recipients, cardiovascular disease (CVD) is the leading cause of death. The relationship of kidney function with CVD outcomes in transplant recipients remains uncertain. We performed a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial to assess risk factors for CVD and mortality in kidney transplant recipients. Following adjustment for demographic, clinical and transplant characteristics, and traditional CVD risk factors, proportional hazards models were used to explore the association of estimated GFR with incident CVD and all‐cause mortality. In 4016 participants, mean age was 52 years and 20% had prior CVD. Mean eGFR was 49±18 mL/min/1.73 m². In 3676 participants with complete data, there were 527 CVD events over a median of 3.8 years. Following adjustment, each 5 mL/min/1.73 m² higher eGFR at levels below 45 mL/min/1.73 m² was associated with a 15% lower risk of both CVD [HR = 0.85 (0.80, 0.90)] and death [HR = 0.85 (0.79, 0.90)], while there was no association between eGFR and outcomes at levels above 45 mL/min/1.73 m². In conclusion, in stable kidney transplant recipients, lower eGFR is independently associated with adverse events, suggesting that reduced kidney function itself rather than preexisting comorbidity may lead to CVD.     

Belatacept Rescue Therapy in Kidney Transplant Recipients With Vascular Lesions: A Case Control Study

Immunosuppression in kidney transplant recipients with decreased graft function and severe histological vascular changes can be particularly challenging. Belatacept could be a valuable option, as a rescue therapy in this context. We report a retrospective case control study comparing a CNI to belatacept switch in 17 patients with vascular damage and low eGFR to a control group of 18 matched patients with CNI continuation. Belatacept switch was performed on average 51.5 months after kidney transplantation (6.2–198 months). There was no difference between the two groups regarding eGFR at inclusion, and 3 months before inclusion. In the “CNI to belatacept switch group,” mean eGFR increased significantly from 23.5 ± 6.7 mL/min/1.73m² on day 0, to 30.4 ± 9.1 mL/min/1.73 m² on month 6 (p < 0.001) compared to the control group, in which no improvement was observed. These results were still significant on month 12. Two patients experienced biopsy‐proven acute rejection. One was effectively treated without belatacept discontinuation. Two patients needed belatacept discontinuation for infection. In conclusion, the remplacement of CNI with belatacept in patients with decreased allograft function and vascular lesions is associated with an improvement in eGFR.     

A Reappraisal of the Bladder Cumulative Method as a Reliable Technique for the Measurement of Glomerular Filtration Rate

In order to quantify the decline in renal function, repeated measurements of GFR are necessary. The conventional procedure is cumbersome and time expending so that alternative clearance techniques are needed. We propose a simple isotopic technique for measuring GFR by ^99mTc-DTPA and external counting of the bladder by gamma camera (bladder cumulative method). This consists in the measurement by external counting of the amount of labelled filtration marker accumulated in the bladder after intravenous bolus injection. In 36 adult patients with all degrees of renal impairment (serum creatinine 0.9–9.3 mg/dL) GFR was measured twice, once by the conventional method (continuous i.v. infusion of the filtration marker and urine collection by spontaneous voiding) and once by the bladder cumulative method. ^99mTc DTPA was used in performing both methods. A satisfactory agreement was found between GFR measured by bladder cumulative method (BCM) and by conventional method (CM). The BCM averaged 60.0 ± 36.7 mL/min and the CM ± SD averaged 62.8 ± 36.6 mL/mm. The ratio BCM/CM ±f SD was 0.95 ± 0.14 (y = 0.94x + 1.14; r = 0.94)

Considering the 17 patients with renal insufficiency (GFR <60 mL/min) an even better agreement between the two methods was found. In these patients the BCM averaged 28.4 ± 17.2 mL/min; the CM averaged 29.1 ± 16.6 mL/min; and the ratio BCM/CM was 0.96 ± 0.08 (y = 1.03x – 1.47; r = 0.99)

The day-to-day variability of BCM, studied in another 11 patients, was lower than that of creatinine clearance (variation coefficient for duplicate measurements: 7.18 ± 6.65 SD for BCM, 15.68 ± 8.80 SD for CM, p <0.01). The bladder cumulative method is a simple procedure for the accurate measurement of GFR, in particular in patients with renal insufficiency. It represents a reliable tool for estimating the decline in renal function.