Estimating baseline creatinine levels based on the kidney parenchymal volume.

BACKGROUND: Acute kidney injury (AKI) diagnosis often lacks a baseline serum creatinine (Cr) value. Our study aimed to create a regression equation linking kidney morphology to function in kidney donors and chronic kidney disease patients. We also sought to estimate baseline Cr in minimal change disease (MCD) patients, a common AKI-predisposing condition. METHODS: We analyzed 119 participants (mean age 60 years, 50% male, 40% donors) with CT scans, dividing them into derivation and validation groups. An equation based on kidney parenchymal volume (PV) was developed in the derivation group and validated in the validation group. We estimated baseline Cr in 43 MCD patients (mean age 45 years, 61% male) using the PV-based equation and compared with their 6 month post-MCD onset Cr values. RESULTS: In the derivation group, the equation for the estimated glomerular filtration rate (eGFR) was: eGFR (mL/min/1.73m2) = 0.375 × PV (cm3) + (- 0.395) × age (years) + (- 2.93) × male sex + (- 13.3) × hypertension + (- 14.0) × diabetes + (- 0.210) × height (cm) + 82.0 (intercept). In the validation group, the eGFR and estimated Cr values correlated well with the measured values (r = 0.46, p = 0.01; r = 0.51, p = 0.004, respectively). In the MCD group, the baseline Cr values were significantly correlated with the estimated baseline Cr values (r = 0.52, p < 0.001), effectively diagnosing AKI (kappa = 0.76, p < 0.001). CONCLUSIONS: The PV-based regression equation established in this study holds promise for estimating baseline Cr values and diagnosing AKI in patients with MCD. Further validation in diverse AKI populations is warranted.

Accelerated involution of germinal center in palatine tonsils in IgA nephropathy.

BACKGROUND: Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for antigen-specific humoral immune responses in the palatine tonsils. Germinal center involution is frequently observed in the palatine tonsils of IgAN (IgAN tonsils). However, the pathogenic significance of these characteristic changes remains unclear. This study aimed to investigate the morphological changes in secondary lymphoid follicles in IgAN tonsils and to evaluate the correlation between the morphometric results and the clinicopathological severity of IgAN. METHODS: The tonsils of age-matched patients with recurrent tonsillitis (RT tonsils) were used as controls. The correlation between the degree of lymphoid follicular involution and histopathological severities in clinical or kidney biopsy was evaluated. RESULTS: In total, 87 patients with IgAN were included (48% male, median age 35 years, median estimated glomerular filtration rate: 74 mL/min/1.73 m2). Compared to RT tonsils, IgAN tonsils showed smaller median sizes of lymphoid follicles and germinal centers (P < 0.001). The relative areas of lymphoid follicles (%LFA) and germinal centers (%GCA) in the total tonsillar tissue were smaller in the IgAN tonsils than in the RT tonsils (P < 0.001). In contrast, the median proportion of mantle zones in the total tonsillar tissue was comparable between the groups. A lower %LFA was associated with a longer period from the onset of urinary abnormalities to biopsy diagnosis and higher urinary protein excretion (P = 0.01). %LFA showed significant negative correlations with frequencies of glomeruli with both global and segmental sclerosis. CONCLUSIONS: The present study confirmed accelerated germinal center involution in the tonsils of patients with IgAN. This characteristic change in the IgAN tonsil correlates with heavy proteinuria and advanced chronic histopathological changes in the kidneys, thereby suggesting the involvement of repeated tonsillar immunoreactions during IgAN progression.

Near-sudden unexpected death in a patient with epilepsy undergoing hemodialysis: a case report.

Sudden unexpected death in epilepsy (SUDEP) has been defined as a sudden/unexpected, witnessed/unwitnessed, nontraumatic, and nondrowning death in epileptic patients with/without seizure evidence and documented status epilepticus. Identified as the leading cause of epilepsy-related deaths, SUDEP cases are highly unrecognized and underreported due to diagnostic difficulty. We report a case of a successfully revived hemodialysis patient who developed cardiopulmonary arrest after a witnessed convulsive seizure. Electroencephalogram revealed epileptic abnormalities. Therefore, this case could be seizure-induced cardiopulmonary arrest and near-SUDEP. Hence, the possibility of SUDEP should be considered even in hemodialysis patients having conventional coronary risk factors for sudden cardiac death.

Renal Damage in Recurrent Atypical Hemolytic Uremic Syndrome Associated with C3 p.Ile1157Thr Gene Mutation.

Patients with atypical hemolytic uremic syndrome (aHUS) associated with a C3 p.Ile1157Thr mutation show a relatively high renal survival and low mortality rates, but renal histopathological findings after recurrence have been rarely reported. A 30-year-old man with a C3 p.Ile1157Thr mutation experienced a third recurrence of thrombotic microangiopathies with neurological and gastrointestinal disorders. A renal biopsy performed during the recovery phase of acute kidney injury revealed collapsed glomeruli and arteriolar vacuolization. Approximately 10% of glomeruli were globally sclerotic, despite the absence of arterio-/arteriolo-sclerosis. These findings suggest substantial progression of irreversible injuries in multiple organs, including kidneys, which occurs in aHUS patients with repeated thrombotic microangiopathies.

Total Nephron Number and Single-Nephron Parameters in Patients with IgA Nephropathy.

Background: Single-nephron dynamics in progressive IgA nephropathy (IgAN) have not been studied. We applied novel methodology to explore single-nephron parameters in IgAN. Methods: Nonglobally sclerotic glomeruli (NSG) and globally sclerotic glomeruli (GSG) per kidney were estimated using cortical volume assessment via unenhanced computed tomography and biopsy-based stereology. Estimated single-nephron GFR (eSNGFR) and single-nephron urine protein excretion (SNUPE) were calculated by dividing eGFR and UPE by the number of NSG. Associations with CKD stage and clinicopathologic findings were cross-sectionally investigated. Results: This study included 245 patients with IgAN (mean age 43 years, 62% male, 45% on renin-angiotensin aldosterone system [RAAS] inhibitors prebiopsy) evaluated at kidney biopsy. CKD stages were 10% CKD1, 43% CKD2, 19% CKD3a, 14% CKD3b, and 14% CKD4-5. With advancing CKD stage, NSG decreased from mean 992,000 to 300,000 per kidney, whereas GSG increased from median 64,000 to 202,000 per kidney. In multivariable models, advancing CKD stage associated with lower numbers of NSG, higher numbers of GSG, and lower numbers of GSG + NSG, indicating potential resorption of sclerosed glomeruli. In contrast to the higher mean glomerular volume and markedly elevated SNUPE in advanced CKD, the eSNGFR was largely unaffected by CKD stage. Lower SNGFR associated with Oxford scores for endocapillary hypercellularity and crescents, whereas higher SNUPE associated with segmental glomerulosclerosis and tubulointerstitial scarring. Conclusions: SNUPE emerged as a sensitive biomarker of advancing IgAN. The failure of eSNGFR to increase in response to reduced number of functioning nephrons suggests limited capacity for compensatory hyperfiltration by diseased glomeruli with intrinsic lesions.

Tonsillectomy Monotherapy for IgA Nephropathy: A Case Series.

RATIONALE & OBJECTIVE: Studies of immunoglobulin A nephropathy (IgAN) have suggested the therapeutic benefit of simultaneously adding tonsillectomy to corticosteroid therapy. However, the efficacy of tonsillectomy monotherapy in the absence of simultaneous use of corticosteroids is unclear. STUDY DESIGN: Patients with IgAN treated with tonsillectomy monotherapy were analyzed retrospectively. Clinical parameters, including kidney function slope, were compared before and after tonsillectomy. SETTING & PARTICIPANTS: Patients with biopsy-proven IgAN who received tonsillectomy monotherapy at our hospital between 2007 and 2018. RESULTS: 20 Japanese patients with IgAN were included in this study (mean follow-up period, 135 months from initial biopsy diagnosis to tonsillectomy). All patients had been treated with renin-angiotensin-aldosterone system inhibitors. 17 patients had a history of induction therapy with corticosteroids. Mean time to tonsillectomy from termination of corticosteroid therapy was 84 months. Hematuria, proteinuria, and clinical remission were achieved in 13 of 17 (76%), 10 of 17 (59%), and 8 of 20 (40%) patients at medians of 3.0, 6.0, and 13.5 months, respectively, after tonsillectomy. The slope of the estimated glomerular filtration rate (eGFR) increased significantly during the 81-month observation period, including the periods before and after tonsillectomy (-2.59 vs 1.05 mL/min/1.73 m2 per year; P < 0.001). The effect on eGFR slope was consistent in 11 patients with reduced GFR (eGFR < 60 mL/min/1.73 m2) at the time of tonsillectomy (-3.07 vs -0.39 mL/min/1.73 m2 per year; P < 0.001). LIMITATIONS: Small sample size. Lack of a control (no-tonsillectomy) group due to the difficulty of setting the baseline time point (which corresponded to tonsillectomy in our sample). Potential exclusion of patients with the most severe disease who are likely to receive corticosteroids. Lack of generalizability to patients in other countries. CONCLUSIONS: Tonsillectomy monotherapy may prevent kidney function decline in some patients with IgAN with kidney disease that has been progressive despite long-term application of conventional therapies.

Nephron Number and Time to Remission in Steroid-Sensitive Minimal Change Disease.

RATIONALE & OBJECTIVE: The response to corticosteroid therapy may differ among patients with minimal change disease (MCD). Previous studies have suggested that glomerular hypertrophy or low areal glomerular density in biopsy specimens, which may be related to fewer nephrons, is associated with such a difference. We examined the associations between nephron number and the therapeutic response to corticosteroids in patients with MCD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 75 adult patients with a histologic diagnosis of MCD. EXPOSURE: Nephron number per kidney estimated based on the combination of unenhanced computed tomography and nonsclerotic volumetric glomerular density in kidney biopsy specimens. OUTCOMES: Complete remission and relapse following corticosteroid therapy. ANALYTICAL APPROACH: Multivariable Cox proportional hazard analyses of associations between factors, including nephron number, and outcomes. RESULTS: Mean age of patients was 45.9 years and 60.0% were men. Patients had an estimated glomerular filtration rate of 64.6 mL/min/1.73 m2 and proteinuria of 8.7 g/d. The estimated total number of nonsclerotic glomeruli ranged from 1.07 to 18.77 ×105 per kidney among all patients. There were no significant differences in total amounts or selectivity of urinary protein excretion at biopsy among the tertile groups categorized by nephron number. All patients responded to corticosteroid therapy, but those with fewer nephrons had a delayed achievement of complete remission. Multivariable Cox proportional hazard analyses identified nephron number as a significant independent explanatory variable for the achievement of complete remission, with a hazard ratio of 1.10 (95% CI, 1.02-1.19)/100,000 nephrons per kidney. Nephron number in these patients was not associated with achievement of partial remission or relapse following complete remission. LIMITATION: Retrospective design and sampling bias of needle biopsy. CONCLUSIONS: A small nephron number in patients with MCD is associated with longer time to complete remission.

Kidney Disease Associated With Anorexia Nervosa: A Case Series With Kidney Biopsies.

RATIONALE & OBJECTIVE: Anorexia nervosa is often intractable and induces various physical disorders, including kidney disease and mineral disorders, occasionally progressing to kidney failure. No consensus-based clinical practice guidelines have been established for patients with anorexia nervosa referred to a nephrologist. STUDY DESIGN: Patients with anorexia nervosa-associated kidney disease diagnosed were analyzed retrospectively. Kidney outcomes were defined as doubling of serum creatinine level and/or progression to end-stage kidney disease. SETTING & PARTICIPANTS: Patients with a history of anorexia nervosa with kidney disease, including electrolyte abnormalities, who were referred to our hospital between 1992 and 2017 were included. RESULTS: 14 female patients were included. The time from anorexia nervosa onset to the initial visit with a nephrologist was 17.8 years. At the first visit, median body mass index was 13.4 kg/m2, median serum creatinine level was 1.9 mg/dL, and median serum potassium level was 2.7 mmol/L. All patients showed hypokalemia and addictive vomiting or diuretic/laxative abuse. During the median observation period of 3.1 years, kidney outcomes occurred in 9 patients, and 2 died due to their anorexia nervosa. 4 patients underwent kidney biopsy. The kidney biopsy findings of these patients included hypertrophy of the juxtaglomerular apparatus, advanced glomerular collapse, and interstitial fibrosis, consistent with ischemic kidney injury and hypokalemic nephropathy. LIMITATIONS: The sample size was small, and kidney function was assessed based on serum creatinine levels in patients with anorexia nervosa with low muscle mass. CONCLUSIONS: Most patients with anorexia nervosa referred to nephrologists had kidney disease at the time of the first visit. Improving kidney outcomes of patients with anorexia nervosa may require earlier collaboration between psychiatrists and nephrologists.