Fatigability: An Early Marker of Diminished Renal Function?

Renal function declines markedly with age due to normal aging and/or disease processes and impacts multiple systems. Diminished renal function may manifest as low exercise tolerance and fatigue threshold. Using data on 951 well-functioning (usual gait speed >.67m/s and no difficulty walking ¼ mile) men and women (51%) aged 60-89 years in the Baltimore Longitudinal Study of Aging, we evaluated the cross-sectional association between perceived fatigability (Rating Perceived Exertion after 5-minute treadmill walk at 1.5mph) categorized as 6-7, 8-9, 10-11 and 12+ and GFR using Cockcroft-Gault. For each fatigability increment, likelihood of suboptimal (GFR=75-89, 21%), diminished (GFR=60-74, 26%) and poor renal function (GFR=15-59, 30%) relative to GFR≥90 was respectively OR(95%CI)p-value 1.51(1.16-1.96).002, 1.38(1.04-1.83).027 and 1.68(1.22-2.31).002 adjusted for demographics, weight, height, smoking, exercise and anemia. Findings were similar for men and women. Perceived fatigability may facilitate identification of apparently well-functioning older adults on the precipice of suboptimal to poor renal function.

A low serum iron level is a potential predictor of poor renal function in patients following laparoscopic sleeve gastrectomy: a retrospective study

This study aimed to assess the association of serum iron level (Iron) with the estimated glomerular filtration rate (eGFR) after bariatric surgery (BS). We reviewed 210 patients with mean age of 39.1 ± 10.6 years (body mass index, 41.4 ± 5.5 kg/m2) undergoing BS. The primary outcome was the relationship between Iron and eGFR at 12-month after surgery. Multiple linear regression analyses were performed using postoperative eGFR as dependent variables and using Iron and other variables (i.e., age) as independent variables. At 12-month follow-up, 94 patients were analyzed. BMI significantly decreased, whereas serum iron level significantly increased. Although the percentage of patients with eGFR of < 90 mL/min/1.73 m2 increased during the study period, no significant difference was found in postoperative 12-month eGFR. No correlations were noted between Iron and eGFR at baseline and postoperative 1 and 6 months, whereas a significant relationship was observed between Iron and postoperative 12-month eGFR. Multiple linear regression analyses revealed that Iron and presence of diabetes were the independent predictors of postoperative 12-month eGFR. This pilot study showed a positive association of postoperative serum iron level with renal function in this patient population. Further large-scale trials are needed to confirm the findings.

Intra-articular administration of vancomycin and tobramycin during primary cementless total knee arthroplasty

Aims Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA. Methods A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml. Results A total of 22 patients were included in final analysis. At one, four, and 24 hours postoperatively, mean (95% confidence interval (CI)) serum concentrations were 2.4 (0.7 to 4.1), 5.0 (3.1 to 6.9), and 4.8 (2.8 to 6.9) for vancomycin and 4.9 (3.4 to 6.3), 7.0 (5.8 to 8.2), and 1.3 (0.8 to 1.8) for tobramycin; intra-articular concentrations were 1,900.6 (1,492.5 to 2,308.8), 717.9 (485.5 to 950.3), and 162.2 (20.5 to 304.0) for vancomycin and 2,105.3 (1,389.9 to 2,820.6), 403.2 (266.6 to 539.7), and 98.8 (0 to 206.5) for tobramycin. Conclusion Intra-articular administration of 1 g of vancomycin and 600 mg of tobramycin as a solution after closure of the arthrotomy in primary cementless TKA achieves therapeutic intra-articular concentrations over the first 24 hours postoperatively and does not reach sustained toxic levels in peripheral blood. Cite this article: Bone Joint J 2021;103-B(11):1702–1708.

Comparison of gemcitabine-based chemotherapies for advanced biliary tract cancers by renal function: an exploratory analysis of JCOG1113

JCOG1113 is a randomized phase III trial in patients with advanced biliary tract cancers (BTCs) (UMIN000001685), and gemcitabine plus S-1 (GS) was not inferior to gemcitabine plus cisplatin (GC). However, poor renal function often results in high toxicity of S-1. Therefore, we examined whether GS can be recommended for patients with low creatinine clearance (CCr). Renal function was classified by CCr as calculated by the Cockcroft-Gault formula: high CCr (CCr ≥ 80 ml/min) and low CCr (80 > CCr ≥ 50 ml/min). Of 354 patients, 87 patients on GC and 91 on GS were included in the low CCr group, while there were 88 patients on GC and 88 patients on GS in the high CCr group. The HR of overall survival for GS compared with GC was 0.687 (95% CI 0.504–0.937) in the low CCr group. Although the total number of incidences of all Grade 3–4 non-haematological adverse reactions was higher (36.0% vs. 11.8%, p = 0.0002), the number of patients who discontinued treatment was not different (14.1% vs. 16.9%, p = 0.679) for GS compared with GC in the low CCr group. This study suggests that GS should be selected for the treatment of advanced BTC patients with reduced renal function.

Renal functional improvement after pediatric pyeloplasty in kidneys with split renal function less than 20%: a single institute experience

Background Pediatric pyeloplasty in ureteropelvic junction obstruction (UPJO) is indicated in renal impaired drainage or renal function deterioration. The improvement of renal function after pediatric pyeloplasty is still controversial in poorly functioning kidneys. Past studies on poorly functioning kidneys had a variable SRF specification, and these studies often had a limited number of patients so that they did not achieve statistical significance. The study aims to detect the renal functional improvement after pediatric Anderson-Hynes pyeloplasty (AHP) with split renal function (SRF) less than 20% (poor renal function). Results A retrospective study included 46 pediatric patients with unilateral UPJO who underwent open AHP with SRF < 20% on a renal isotope scan from August 2012 to October 2018. Success was defined based on either improvement in symptoms, improvement in drainage on postoperative renography, and/or improvement or stability in SRF on the renal scan done 6 months postoperatively and yearly thereafter. Deterioration of SRF by more than 5% was deemed to be deterioration. An increase in SRF of more than 5% was deemed to be an improvement. A total of 46 patients with a mean age of 32 months with poor renal function on isotope renogram (SRF < 20%) were included. All patients had an obstructive pattern on the preoperative radionuclide scans. The median preoperative SRF was 9.26%. The mean (range) follow-up was 30 months. The success rate was 91.3%. Three patients underwent redo pyeloplasty, whereas a secondary nephrectomy was necessary for one. The remaining (42) patients showed stability or improvement of SRF with no further symptoms. Renal scintigraphy at 6 and 12 months after surgery revealed significantly increased SRF compared to preoperative one. Conclusion Poorly functioning renal unit with SRF < 20% can show functional improvement and recoverability after pediatric pyeloplasty.

Treatment With Vasopressor Agents for Cardiovascular Shock Patients With Poor Renal Function; Results From the Japanese Circulation Society Cardiovascular Shock Registry

According to the guidelines for cardiogenic shock, norepinephrine is associated with fewer arrhythmias than dopamine and may be the better first-line vasopressor agent. This study aimed to evaluate the utility of norepinephrine vs. dopamine as first-line vasopressor agent for cardiovascular shock depending on the presence and severity of renal dysfunction at hospitalization. This was a secondary analysis of the prospective, multicenter Japanese Circulation Society Cardiovascular Shock Registry (JCS Shock Registry) conducted between 2012 and 2014, which included patients with shock complicating emergency cardiovascular disease at hospital arrival. The analysis included 240 adult patients treated with norepinephrine alone (n = 98) or dopamine alone (n = 142) as the first-line vasopressor agent. Primary endpoint was mortality at 30 days after hospital arrival. The two groups had similar baseline characteristics, including estimated glomerular filtration rate (eGFR), and similar 30-day mortality rates. The analysis of the relationship between 30-day mortality rate after hospital arrival and vasopressor agent used in patients categorized according to the eGFR-based chronic kidney disease classification revealed that norepinephrine as the first-line vasopressor agent might be associated with better prognosis of cardiovascular shock in patients with mildly compromised renal function at admission (0.0 vs. 22.6%; P = 0.010) and that dopamine as the first-line vasopressor agent might be beneficial for cardiovascular shock in patients with severely compromised renal function [odds ratio; 0.22 (95% confidence interval 0.05–0.88; P = 0.032)]. Choice of first-line vasopressor agent should be based on renal function at hospital arrival for patients in cardiovascular shock.Clinical Trial Registration:http://www.umin.ac.jp/ctr/, Unique identifier: 000008441.

Undernutrition when young and the risk of poor renal function in adulthood in women with diabetes in Shanghai, China

Objective To evaluate the effect of undernutrition when young on the risk of poor renal function in adulthood in women with diabetes mellitus. Methods We studied diabetic women born between 1921 and 1958 who were exposed to the 1959-to-1962 Chinese famine when they were 0 to 37 years old. Exposure age was classified as young adulthood (18 to 37 years), adolescence (10 to 17 years), or childhood (0 to 9 years). The Adolescence group, which was provided with the largest amount of food during the famine, was used as the control group, and variance and binary logistic regression analyses were performed. Results The prevalences of low estimated glomerular filtration rate (eGFR) in the Childhood, Adolescence, and Young adulthood groups were 5.26%, 22.39%, and 79.24%, respectively. The risk of low eGFR for the Young adulthood group (odds ratio [OR] 1.65, 95% confidence interval [CI] 1.10, 2.48), but not for the Childhood group (OR 1.10, 95% CI 0.68, 1.78), was higher than that for the Adolescence group after adjustment for potential confounders. Conclusions Undernutrition during young adulthood significantly increases the risk of renal dysfunction in adult women with diabetes. Therefore, the nutrition of less affluent young women should be improved.

Outcome Predictors of Biopsy-Proven Myeloperoxidase-Anti-Neutrophil Cytoplasmic Antibody-Associated Glomerulonephritis

ObjectiveTo determine the prognostic values of histopathologic classification of myeloperoxidase-anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis and other clinical and laboratory features at the time of presentation on renal and patient survival associated with myeloperoxidase-ANCA-associated glomerulonephritis (MPO-ANCA-GN).MethodsA total of 112 patients diagnosed with MPO-ANCA-GN from October 2005 to December 2018 were enrolled. The baseline clinical characteristics, renal histopathological data, and risk factors predictive of renal and patient survival were retrospectively analyzed.ResultsAll 112 patients underwent renal biopsy. Disease in 32 patients was classified as focal, 26 as mixed, 29 as crescentic, and 25 as sclerotic. Over a median follow-up period of 41.5 months, there were 44 patients dialysis-dependent. The renal survival rate was significantly higher in the focal group than the other groups (p &lt; 0.001) and significantly lower in the sclerotic group (p &lt; 0.05). In addition, disease histopathologically classified as sclerotic (p = 0.044), high serum creatinine level (≥320 μmol/L, p &lt; 0.001), low albumin (&lt;30 g/L, p = 0.024) and hemoglobin level (&lt;90 g/L, p = 0.044) were associated with a greater risk of ESRD. After follow-up, 70 (62.5%) of 112 patients survived. Old age (≥60 years, p = 0.018) and low serum albumin (&lt;30 g/L, p = 0.006) was significant risk factor for patient survival.ConclusionAmong patients with MPO-ANCA-GN, those with poor renal function, disease histopathologically classified as sclerotic, and lower albumin and hemoglobin levels were risk factors for ESRD, while older age and low serum albumin level were associated with a greater risk for all-cause mortality.

Advanced Chronic Kidney Disease with Low and Very Low GFR: Can a Low-Protein Diet Supplemented with Ketoanalogues Delay Dialysis?

Background: Previous studies have demonstrated that dietary therapy can delay the initiation of dialysis, but little research has investigated whether patients with very poor renal function would benefit from a dietary therapy. Methods: This study was performed by using the Chang Gung Research Database (CGRD), which is based on the largest medical system in Taiwan. Patients with estimated glomerular filtration rates (eGFR) < 15 mL/min/1.73 m2 between 2001 and 2015 with more than 3 months of low-protein diet supplemented with ketoanalogues (sLPD) were extracted (Ketosteril group). We then assigned five patients without any sLPD to match one patient of the Ketosteril group (comparison group). Both groups were followed up for 1 year for the initiation of dialysis and rates of major adverse cardiac and cerebrovascular events (MACCEs). Results: The Ketosteril group (n = 547), compared with the comparison group (n = 2735), exhibited a lower incidence of new-onset dialysis (40.2% vs. 44.4%, subdistribution hazard ratio (SHR): 0.80, 95% confidence interval (CI): 0.70–0.91) and MACCEs (3.7% vs. 5.9%, HR: 0.61, 95% CI: 0.38–0.97). The beneficial effect of an sLPD did not differ in patients with a baseline eGFR < 5 mL/min/1.73 m2. Conclusion: Even among patients with extremely low eGFR, sLPD treatment can safely delay the need for dialysis.

Severe and prolonged hypocalcemia after a single dose of denosumab for metastatic breast cancer with diffuse bone involvement without prior calcium/vitamin D supplementations

Introduction Denosumab is a human monoclonal antibody antiresorptive agent used for the treatment of bone metastasis in different cancer types, including breast cancer. Hypocalcemia is a known adverse effect of denosumab, and early supplementation plays an important role in the prevention and management of hypocalcemia. Case report A 63-year-old female with stage IV estrogen receptor-positive breast cancer with diffuse bone metastasis experienced severe, prolonged hypocalcemia following a single dose of denosumab. The patient also had several risk factors for denosumab-associated hypocalcemia. Despite not receiving additional doses of denosumab, the patient required multiple hospitalizations and outpatient infusions of calcium to resolve her symptomatic hypocalcemia. Management and outcome: Severe hypocalcemia associated with denosumab can be prevented or mitigated by recognizing the risk factors for hypocalcemia and supplementing with vitamin D/calcium. Proposed risk factors include poor renal function, hypoparathyroidism, insufficient calcium intake, and diffuse metastatic bone disease. Studies suggest that early supplementation before starting denosumab can lower this risk. Discussion Several cases of severe hypocalcemia associated with denosumab have been reported. However, to the authors’ knowledge, this is the first report that highlights the importance of early vitamin D/calcium supplementations for a patient with diffuse metastatic bone disease with pre-existing low levels of calcium.