Relationships among Non-Neoplastic Histopathological Features, Kidney Function, Proteinuria, and Other Clinical Factors in Patients Undergoing Nephrectomy.

Introduction: The non-neoplastic kidney parenchyma from nephrectomies is often overlooked in routine examinations. We aimed to evaluate the associations between global glomerulosclerosis (GS), interstitial fibrosis (IF), or arteriosclerosis (AS) and estimated glomerular filtration rate (eGFR), dipstick proteinuria, and other clinical factors. Methods: We performed a cross-sectional analysis of 781 patients with nephrectomy. We used regression models with and without interaction factors. The tested exposures were GS, IF, or AS, and the outcome measures were GFR and dipstick proteinuria. Results: In multivariable analyses, increasing degrees of GS, IF, or AS were significantly associated with lower eGFR and proteinuria (p < 0.05 for each). Obesity and hypertension (HTN) modified the association between eGFR and degrees of GS, whereas proteinuria and cardiovascular disease (CVD) modified the association between eGFR and degrees of AS (p for interaction <0.05). Compared with GS <10%, GS >50% was associated with lower eGFR in patients with (-45 mL/min/1.73 m2) than without (-19 mL/min/1.73 m2) obesity, and GS >50% was associated with lower eGFR in patients with (-31 mL/min/1.73 m2) than without (-16 mL/min/1.73 m2) HTN. Compared with AS <26%, AS >50% was associated with lower eGFR in patients with (-11 mL/min/1.73 m2) than without (-6 mL/min/1.73 m2) proteinuria, and AS >50% was associated with lower eGFR in patients with (-23 mL/min/1.73 m2) than without (-7 mL/min/1.73 m2) CVD. Conclusion: Greater degrees of each GS, IF, and AS are independently associated with proteinuria and lower eGFR. Obesity, HTN, proteinuria, and CVD modify the relationship between eGFR and specific histopathological features of nephrosclerosis.

One-year all-cause mortality in hospitalized patients with COVID-19 and end-stage renal disease undergoing hemodialysis.

INTRODUCTION: Patients with end-stage renal disease (ESRD) on dialysis and COVID-19 infection have an increased risk of in-hospital mortality, but whether these patients have a higher long-term mortality risk is unknown. MATERIALS AND METHODS: Retrospective chart review of 958 patients admitted with COVID-19 infection or those with ESRD admitted for any other reason between February 2020 and August 2020. We collected data on demographics, comorbidities, laboratory tests, and mortality. The primary outcome was all-cause 1-year mortality. The secondary outcome was in-hospital mortality. We used primarily logistic regression models to assess the mortality risk. RESULTS: In total, 651 patients without ESRD with COVID-19 (COVID+ESRD-), 259 with ESRD without COVID-19 (ESRD+COVID-), and 48 with ESRD with COVID-19 (COVID+ESRD+) were hospitalized between February 2020 and August 2020. Patients were followed after discharge until September 2021. The all-cause 1-year mortality rates were 24% in patients with COVID+ESRD-, 22% in ESRD+COVID- patients, and 40% in those with COVID+ESRD+ (p < 0.05). Compared to the COVID+ESRD- group, the unadjusted and adjusted odds ratio (OR) for all-cause 1-year mortality in the COVID+ESRD+ group was 2.13 (95% confidence interval (CI), 1.16 - 3.91) and 2.15 (95% CI,1.12 - 4.14), respectively. The unadjusted and adjusted OR for all-cause in-hospital mortality in the COVID+ESRD+ group was 1.79 (95% CI, 0.92 - 3.49); and 1.79 (95% CI, 0.88 - 3.65), respectively. We found no statistically significant difference between the COVID+ESRD- and ESRD+COVID- groups for both in-hospital and 1-year mortality (p > 0.05). CONCLUSION: Patients with COVID+ESRD+ have significantly higher odds for all-cause 1-year mortality compared to COVID+ESRD- patients. Future studies should investigate the mechanisms of long-term mortality risk in ESRD patients with COVID-19 infection.

COVID-19 in a patient with end-stage renal disease on chronic in-center hemodialysis after evidence of SARS-CoV-2 IgG antibodies. Reinfection or inaccuracy of antibody testing.

A patient with end-stage renal disease on hemodialysis with a previous positive SARS-CoV-2 IgG antibody was diagnosed with severe COVID-19. Issues regarding reinfection, the potential lack of antibody protection after asymptomatic infection, the possibility of antibody dependent enhancement and careful interpretation of antibody test results are discussed.

Inflammation and elevated levels of fibroblast growth factor 23 are independent risk factors for death in chronic kidney disease.

Inflammation is a consequence of chronic kidney disease (CKD) and is associated with adverse outcomes in many clinical settings. Inflammation stimulates production of fibroblast growth factor 23 (FGF23), high levels of which are independently associated with mortality in CKD. Few large-scale prospective studies have examined inflammation and mortality in patients with CKD, and none tested the interrelationships among inflammation, FGF23, and risk of death. Therefore, we conducted a prospective investigation of 3875 participants in the Chronic Renal Insufficiency Cohort (CRIC) study with CKD stages 2 to 4 to test the associations of baseline plasma interleukin-6, high-sensitivity C-reactive protein, and FGF23 levels with all-cause mortality, censoring at the onset of end-stage renal disease. During a median follow-up of 6.9 years, 550 participants died (20.5/1000 person-years) prior to end-stage renal disease. In separate multivariable-adjusted analyses, higher levels of interleukin-6 (hazard ratio per one standard deviation increase of natural log-transformed levels) 1.35 (95% confidence interval, 1.25-1.46), C-reactive protein 1.28 (1.16-1.40), and FGF23 1.45 (1.32-1.60) were each independently associated with increased risk of death. With further adjustment for FGF23, the risks of death associated with interleukin-6 and C-reactive protein were minimally attenuated. Compared to participants in the lowest quartiles of inflammation and FGF23, the multivariable-adjusted hazard ratio of death among those in the highest quartiles of both biomarkers was 4.38 (2.65-7.23) for interleukin-6 and FGF23, and 5.54 (3.04-10.09) for C-reactive protein and FGF23. Thus, elevated levels of interleukin-6, C-reactive protein, and FGF23 are independent risk factors for mortality in CKD.

Diuretics, Limited Ultrafiltration, and Residual Renal Function in Incident Hemodialysis Patients: A Case Series.

The effect of diuretics on residual renal function expressed as residual GFR (rGFR) and urine volume (rUV) using 24-hour urine collections has not been well examined in hemodialysis (HD) patients. We present a small (seven patient) but provocative case series describing a strikingly low rate of decline in rUV and rGFR (average of creatinine and urea clearances, 24-hour urine collections) in patients treated with increasing doses of furosemide (up to 360 mg/day) during the first 2 years after initiation of HD. Between 6 and 12 months, the mean rUV fell by 1 ml/month, whereas rGFR declined by 0.03 ml/min/1.73 m(2) /month. The mean rate of decline from 12 to 24 months for rUV (33 ml/month) and rGFR (0.02 ml/min/1.73 m(2) /month) were also low. While data are clearly limited and the observation retrospective, they are consistent with the better documented benefit of diuretics observed in end-stage renal disease patients treated with peritoneal dialysis.

Dialysate Sodium: Choosing the Optimal Hemodialysis Bath.

Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and is a major cause of hospitalizations. It is often addressed by reinforcing the importance of a low-salt diet with patients and challenging estimated dry weights. More recently, interest has shifted toward the dialysate sodium prescription as a strategy to improve fluid overload and its adverse sequelae. The availability of high-flux high-efficiency dialysis in conjunction with the need to ensure its tolerability for patients has resulted in an increase in dialysate sodium prescriptions from 120 to ≥140 mEq/L. However, we are now tackling the unforeseen consequences associated with high dialysate sodium prescriptions. High dialysate sodium concentration is associated with high interdialytic weight gain, a commonly used surrogate for hypervolemia contributing to hypertension. The association between mortality and high dialysate sodium concentration remains controversial with conflicting data. It is clear that fluid management in the diverse end-stage renal disease population is extremely complex and more clinical trials are needed. In the meantime, while patients require treatments and clinical decisions need to be made, this review article attempts to summarize the current evidence for individualized dialysate sodium prescriptions based on patients' volume status, comorbid conditions, plasma sodium level, and hemodynamic response to dialysis therapy.

Comparison of mortality of ESRD patients with lupus by initial dialysis modality.

BACKGROUND AND OBJECTIVES: Little is known regarding whether mortality among ESRD patients with SLE differs between those initiating with peritoneal dialysis (PD) versus hemodialysis (HD). This study compared the mortality risk of ESRD patients with SLE initiating with PD versus HD after matching their baseline sociodemographic and clinical factors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Of 11,023 ESRD patients with SLE initiating dialysis with PD or HD between 1995 and 2006 with complete records in the US Renal Data System, 1352 pairs were matched on 13 predictors utilizing a predicted probability of group membership into the PD group using propensity score matching. The primary outcome was overall mortality. Secondary outcomes were cardiovascular-related and infection-related mortality. Outcomes were compared between groups with survival statistics. The period of observation ended on December 31, 2009. The median follow-up was 3 years. RESULTS: Matched pairs were predominantly women (86%) with a median age of 39 years. Matched pairs had a balance (P ≥ 0.05) of all baseline factors. Matched pairs had a similar risk of overall mortality (hazard ratio, 0.96 [95% confidence interval, 0.82 to 1.13]; mortality, 21.4% [290 to 1352] versus 22.5% [304 to 1352] for PD versus HD) within the first 3 years of observation. Matched pairs also had similar cardiovascular-related mortality (10.5% versus 9.5% for PD versus HD) and infection-related mortality (3% versus 4.4% for PD versus HD). CONCLUSIONS: In ESRD patients with SLE, the mortality was similar among those initiating with PD versus HD after predictors were matched between groups.

Individualized reduction in dialysate sodium in conventional in-center hemodialysis.

Recent studies have focused on the association between dialysate sodium (Na(+)) prescriptions and interdialytic weight gain (IDWG). We report on a case series of 13 patients undergoing conventional, thrice-weekly in-center hemodialysis with an individualized dialysate Na(+) prescription. Individualized dialysate Na(+) was achieved in all patients through a stepwise weekly reduction of the standard dialysate Na(+) prescription (140 mEq/L) by 2-3 mEq/L until reaching a Na(+) gradient of -2 mEq/L (dialysate Na(+) minus average plasma Na(+) over the preceding 3 months). Interdialytic weight gain, with and without indexing to dry weight (IDWG%), blood pressure, and the proportion of treatments with cramps, intradialytic hypotension (drop in systolic blood pressure >30 mmHg) and intradialytic hypotension requiring an intervention were reviewed. At the beginning of the observation period, the pre-hemodialysis (HD) plasma Na(+) concentration ranged from 130 to 141 mEq/L. When switched from the standard to the individualized dialysate Na(+) concentration, IDWG% decreased from 3.4% ± 1.6% to 2.5% ± 1.0% (P = 0.003) with no change in pre- or post-HD systolic or diastolic blood pressures (all P > 0.05). We found no significant change in the proportion of treatments with cramps (6% vs. 13%), intradialytic hypotension (62% vs. 65%), or intradialytic hypotension requiring an intervention (29% vs. 33%). Individualized reduction of dialysate Na(+) reduces IDWG% without significantly increasing the frequency of cramps or hypotension.

Fibroblast growth factor 23 and Inflammation in CKD.

BACKGROUND AND OBJECTIVES: Levels of fibroblast growth factor 23 (FGF23) and inflammatory markers are commonly elevated in CKD, and each is associated with adverse clinical outcomes. This study tested the hypothesis that FGF23 is independently associated with inflammation in CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The association between levels of FGF23 and the inflammatory markers IL-6, C-reactive protein (CRP), TNF-α, and fibrinogen was assessed in a cross-sectional analysis of 3879 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study between June 2003 and September 2008. RESULTS: FGF23 correlated directly with IL-6 (r=0.4), CRP (r=0.2), TNF-α (r=0.4), and fibrinogen (r=0.3; P<0.001 for each). In univariate and multivariable-adjusted linear regression analyses, natural log (ln) transformed FGF23 was significantly associated with lnIL-6, lnCRP, lnTNF-α, and fibrinogen (P<0.001 for each). Each unit higher lnFGF23 was associated with severe inflammation, defined as levels of all inflammatory markers in the highest 25th percentile, in univariate (odds ratio [OR], 2.4 [95% confidence interval (CI), 2.0-2.9]) and multivariable-adjusted (OR, 2.0 [95% CI, 1.6-2.5]) logistic regression analyses. Ascending FGF23 quartiles were independently associated with severe inflammation (OR, 5.6 for the highest versus lowest FGF23 quartile [95% CI, 2.3-13.9]; P for trend < 0.001). CONCLUSIONS: Higher FGF23 levels are independently associated with higher levels of inflammatory markers in patients with CKD and with significantly greater odds of severe inflammation. Future studies should evaluate whether inflammation modifies the association between FGF23 and adverse outcomes in CKD.

Effect of lowering dialysate sodium concentration on interdialytic weight gain and blood pressure in patients undergoing thrice-weekly in-center nocturnal hemodialysis: a quality improvement study.

BACKGROUND: Patients on in-center nocturnal hemodialysis therapy typically experience higher interdialytic weight gain (IDWG) than patients on conventional hemodialysis therapy. We determined the safety and effects of decreasing dialysate sodium concentration on IDWG and blood pressure in patients on thrice-weekly in-center nocturnal hemodialysis therapy. STUDY DESIGN: Quality improvement, pre-post intervention. SETTINGS & PARTICIPANTS: 15 participants in a single facility. QUALITY IMPROVEMENT PLAN: Participants underwent three 12-week treatment phases, each with different dialysate sodium concentrations, as follows: phase A, 140 mEq/L; phase B, 136 or 134 mEq/L; and phase A(+), 140 mEq/L. Participants were blinded to the exact timing of the intervention. OUTCOMES: IDWG, IDWG/dry weight (IDWG%), and blood pressure. MEASUREMENTS: Outcome data were obtained during the last 2 weeks of each phase and compared with mixed models. The fraction of sessions with adverse events (eg, cramping and hypotension) also was reported. RESULTS: IDWG, IDWG%, and predialysis systolic blood pressure decreased significantly by 0.6 ± 0.6 kg, 0.6% ± 0.8%, and 8.3 ± 14.9 mm Hg, respectively, in phase B compared with phase A (P < 0.05 for all comparisons). No differences in predialysis diastolic and mean arterial or postdialysis blood pressures were found (P > 0.05 for all comparisons). The proportion of treatments with intradialytic hypotension was low and similar in each phase (P = 0.9). In phase B compared with phase A, predialysis plasma sodium concentration was unchanged (P > 0.05), whereas postdialysis plasma sodium concentration decreased by 3.7 ± 1.9 mEq/L (P < 0.05). LIMITATIONS: Modest sample size. CONCLUSION: Decreasing dialysate sodium concentrations in patients undergoing thrice-weekly in-center nocturnal hemodialysis resulted in a clinical and statistically significant decrease in IDWG, IDWG%, postdialysis plasma sodium concentration, and predialysis systolic blood pressure without increasing adverse events. Prolonged exposure to higher than required dialysate sodium concentrations may drive IDWG and counteract some of the purported benefits of "go-slow" (longer session length) hemodialysis.

Dialysate sodium and sodium gradient in maintenance hemodialysis: a neglected sodium restriction approach?

BACKGROUND: A higher sodium gradient (dialysate sodium minus pre-dialysis plasma sodium) during hemodialysis (HD) has been associated with sodium loading; however, its role is not well studied. We hypothesized that a sodium dialysate prescription resulting in a higher sodium gradient is associated with increases in interdialytic weight gain (IDWG), blood pressure (BP) and thirst. METHODS: We conducted a cross-sectional study on 1084 clinically stable patients on HD. A descriptive analysis of the sodium prescription was performed and clinical associations with sodium gradient were analyzed. RESULTS: The dialysate sodium prescription varied widely across dialysis facilities, ranging from 136 to 149 mEq/L, with a median of 140 mEq/L. The mean pre-HD plasma sodium was 136.7 ± 2.9 mEq/L, resulting in the majority of subjects (n = 904, 83%) being dialyzed against a positive sodium gradient, while the mean sodium gradient was 4.6 ± 4.4 mEq/L. After HD, the plasma sodium increased in nearly all patients (91%), reaching a mean post-HD plasma sodium of 141.3 ± 2.5 mEq/L. We found a direct correlation between IDWG and sodium gradient (r = 0.21, P < 0.0001). After adjustment for confounders and clustering by facilities, the sodium gradient was independently associated with IDWG (70 g/mEq/L, P < 0.0001). There were no significant associations among sodium gradient and BP, whether measured as pre-HD systolic (r = -0.02), diastolic (r = -0.06) or mean arterial pressure (r = -0.04). Post-HD thirst was directly correlated with sodium gradient (r = 0.11, P = 0.02). CONCLUSION: Sodium gradient is associated with statistically significant and clinically meaningful differences in IDWG in stable patients on HD.

Hyperparathyroidism with hypercalcaemia in chronic kidney disease: primary or tertiary?

Objective . This study aims to highlight the challenges in the diagnosis of hyperparathyroidism (HPT) in patients with advanced chronic kidney disease (CKD). Methods . In this report, we describe a middle-aged Filipino gentleman with underlying CKD who presented with intractable nausea, vomiting, severe and medically refractory hypercalcaemia and parathyroid hormone (PTH) concentrations in excess of 2400 pg/mL. The underlying pathophysiology as well as the aetiologies and current relevant literature are discussed. We also suggest an appropriate diagnostic approach to identify and promptly treat patients with CKD, HPT and hypercalcaemia. Results . Evaluation confirmed the presence of a large parathyroid adenoma; HPT and hypercalcaemia resolved rapidly following resection. Conclusion . This case report is remarkable for its severe hypercalcaemia requiring haemodialysis, large adenoma size, acute-on-chronic kidney injury and markedly elevated PTH concentration in association with primary HPT in CKD.