While a few studies have investigated renal manifestations associated with mitochondrial DNA (mtDNA) mutations, detailed renal histopathological changes and long-term outcomes remain poorly characterized. This study reported a family in which all the five siblings presented with hyperuricemia and chronic kidney disease (CKD); the proband died of kidney failure at 16 years of age, while both parents were unaffected. Renal histology from three siblings revealed multiple foci of sclerotic and atubular glomeruli, as well as focal tubular atrophy, making early pathological diagnosis challenging. Ten years later, whole-exome sequencing identified an m.616T>C mutation in the MT-TF gene of mtDNA, confirming the diagnosis of mitochondrial tubulointerstitial kidney disease and demonstrating mitochondrial abnormalities in the distal tubules and collecting duct. Over a 12-year follow-up period, one patient died of kidney failure, one required dialysis, two progressed from CKD stage G2 to G4, and one remained stable at CKD stage G3. This 12-year study of a family with MT-TF m.616T>C-associated mitochondrial tubulointerstitial kidney disease highlights the relative homogeneity of renal pathology alongside marked heterogeneity in long-term outcomes, despite an identical genetic background.
RATIONALE & OBJECTIVE:Chronic kidney disease (CKD) is a major cause of death in Mexico and blood pressure (BP) may be an important contributor. This study investigated the associations of BP with CKD, albuminuria, and death from kidney failure. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:133,470 adults aged ≥35 to <85 years without CKD or other chronic disease (except diabetes), recruited from two districts of Mexico City between 1998 and 2004, and who survived ≥5 years after recruitment. A random subset of 9198 underwent additional evaluation 2015-2019. EXPOSURES:Systolic BP (SBP), diastolic BP (DBP) and hypertension (participant report of taking blood pressure lowering medication or BP ≥140/90 mm Hg). OUTCOMES:Kidney failure mortality during follow-up, and CKD (self-report and/or eGFR <60 mL/min/1.73m2) and albuminuria at the time of repeat clinical evaluation. ANALYTICAL APPROACH:Multivariable Cox regression for the association of BP with kidney failure mortality and multivariable logistic regression for the association of baseline BP with CKD and albuminuria at the time of re-evaluation. RESULTS:Among all participants, SBP showed a continuous "log-linear" association with kidney failure mortality; each 20 mm Hg lower SBP being associated with 24% lower risk at ages 40-84 years (kidney failure death hazard ratio [HR] 0.76, 95% confidence interval 0.69-0.84). The association was stronger among those without diabetes (HR 0.54, 0.45-0.69) than with diabetes (HR 0.90, 0.80-1.01) but the absolute excess risk associated with higher BP was similar in these subgroups. Hypertension accounted for 9% of kidney failure deaths. Among those re-evaluated, 6% had developed CKD and 25% had albuminuria. 20 mm Hg lower baseline SBP was associated with 24% lower odds of both CKD (odds ratio [OR] 0.76, 0.68-0.85) and albuminuria (OR 0.76, 0.68-0.84) at the time of re-evaluation. Results were similar for DBP. LIMITATIONS:Baseline urine samples were unavailable and kidney function trends over time could not be assessed. CONCLUSIONS:This large prospective study in Mexican adults highlights elevated BP as a major modifiable risk factor for kidney failure mortality, CKD, and albuminuria.
Although mineralocorticoid receptor (MR) antagonism is a mechanistically plausible target of therapy in patients with kidney failure, prior small trials failed to elucidate the safety and efficacy of spironolactone and eplerenone in this population. More conclusive evidence was provided by the ALCHEMIST and ACHIEVE trials, in which spironolactone was not superior to placebo in improving cardiovascular outcomes in patients with kidney failure. The incidence of moderate hyperkalemia in these trials was higher with spironolactone than with placebo. Accordingly, the use of spironolactone or eplerenone for cardiovascular protection in this population is not justified by the currently available clinical-trial data.
Expansion of living kidney donation is needed to meet the increasing global need for kidney replacement therapy. Advances in the understanding of post donation health outcomes have confirmed that living donation in carefully selected donors is associated with low absolute risk of kidney failure of 50 per 10,000 after 20 years. However, information about lifetime risks, heterogeneity of risk, and the long-term safety of donors with pre-donation or post-donation chronic kidney disease (CKD) risk factors remains incomplete. This uncertainty likely contributes to the global stagnation in living donor kidney transplantation. This review outlines the evolution of living kidney donor risk assessment including the exclusion of hyperfiltration injury as a significant contributor to kidney failure after donation and the importance of post-donation CKD risk factor and acute kidney injury as key determinants of post-donation kidney health. Given the low absolute risk of kidney failure the review will identify policy and practice considerations needed to safely expand living kidney donation. Dedicated funding for post donation care to ensure the optimal management of conditions that might compromise post donation kidney function, and to facilitate the ascertainment of information to better inform current and future living kidney donors should be prioritized.
RATIONALE & OBJECTIVE:There is a lack of consensus on the key elements needed to foster clear and effective clinical communication after an episode of inpatient acute kidney injury (AKI). This study sought to achieve consensus on key elements of AKI communication between inpatient and outpatient healthcare professionals. STUDY DESIGN:Three sequential rounds of a modified Delphi process to develop, refine, and achieve consensus on items for inclusion in standardized post-AKI clinical communications. Each round included a survey followed by a virtual discussion. SETTINGS & PARTICIPANTS:Forty-seven participants from 12 countries were recruited through purposive and snowball sampling, including 33 physicians (27 nephrologists), 10 allied health practitioners, and 4 patients and/or caregivers. ANALYTIC APPROACH:Quantitative data were summarized using counts and percentages. Qualitative content analysis was performed to capture additional themes. Consensus recommendations (≥80% agreement) and qualitative findings were iteratively integrated into a draft guide. RESULTS:Participants strongly agreed that post-AKI communication between health care teams should focus on medication changes and describe the trends in serum creatinine. For patients requiring dialysis at discharge, the dates dialysis began and was last administered should be reported. Topics of post-AKI communication by clinicians to patients should focus on medication changes as well as follow-up testing and clinical monitoring. Qualitative evaluation highlighted that the effectiveness of a post-AKI clinical communication guide is dependent on the systematic reporting of clinical information, the provision of actionable guidance for health care professionals and patients, and the monitoring for kidney recovery. LIMITATIONS:Potentially limited generalizability because participants were mostly health care practitioners from high resource healthcare settings. CONCLUSIONS:A multidisciplinary panel of stakeholders reached consensus on key elements of post-AKI clinical communication. The recommendations may valuably inform post-AKI care.
RATIONALE & OBJECTIVE:Autoantibodies targeting complement factor B (anti-FB) are among the most recently described alternative pathway anomalies. Although they have been strongly associated with post-infectious glomerulonephritis in children, the clinical phenotypes associated with such antibodies, along with their effects on the alternative pathway in adults, remain elusive and require further characterization, which was the goal of this study. STUDY DESIGN:Retrospective case series. SETTING & PARTICIPANTS:Patients for whom anti-FB IgG was systematically detected by the French reference center for complement abnormalities between October 2017 and June 2020 and who underwent concurrent kidney biopsy confirming kidney disease were included as cases. FINDINGS:Seventy-one patients tested positive for anti-FB antibodies using ELISA and single-bead antigen assays in the setting of newly diagnosed biopsy-proven kidney disease. Detection of both anti-FB and anti-C3b autoantibodies occurred for 36/71 (51%) patients. In vitro, total purified IgG from these patients enhanced alternative pathway activity, with anti-FB titers being correlated with C3bB proconvertase formation (R2 = 0.40, p < 0.001) and anti-C3b titers being correlated with C3bBb convertase stabilization (R2 = 0.46, p < 0.001), suggesting distinct and potentially synergistic functional effects. Clinically, the most frequent diagnosis associated with anti-FB detection was infection-related glomerulonephritis (IR-GN) (46/71 - 65%), with higher anti-FB titers in patients with IR-GN compared to those with other diagnoses (median 791 [IQR 287-2000] vs. 326 [173-790] AU/mL; Hodges-Lehmann difference 354 AU/mL [95% CI: 58-1020]; p = 0.01). No difference was detected in anti-C3b titers between IR-GN and other diagnoses. Anti-FB antibodies became undetectable in 21 of 36 retested patients (58%); among the 10 patients with persistent detection beyond 3 months, 8 (80%) had uncontrolled infection. After a median follow-up of 12.5 (5-24) months, 18/67 (27%) patients experienced a major adverse kidney event (kidney failure or a sustained >50 decline in eGFR below the baseline value). LIMITATIONS:Retrospective design, the series was enriched in alternative pathway anomalies due to reference center recruitment. CONCLUSIONS:Detection of anti-FB antibodies is strongly associated with infection-related glomerulonephritis in adult patients, highlighting an important mechanism of alternative pathway deregulation in such diseases. PLAIN LANGUAGE SUMMARY:Antibodies targeting factor B, a key protein of the complement cascade, have been shown to activate the complement system and promote kidney inflammation. However, the clinical characteristics and outcomes of patients with such autoantibodies remain largely understudied, particularly in adults. This study systematically screened over 700 adults referred for complement investigation and identified 71 patients with anti-factor B antibodies and concurrent biopsy-proven kidney disease. These antibodies were predominantly associated with infection-related glomerulonephritis, activated the alternative complement pathway, and tended to disappear once the underlying infection was controlled. These findings highlight the importance of screening for anti-factor B antibodies in patients with complement-mediated kidney disease, as their detection may prompt the search for an underlying infection and guide therapeutic decisions.
The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus Nephritis (LN). The management of LN has become increasingly individualized, and treatment options are expanding; for example, since the release of the KDIGO guideline, the US Food and Drug Administration has approved obinutuzumab in addition to belimumab and voclosporin for the treatment of LN, and the enrollment of patients in chimeric antigen receptor (CAR) T-cell therapy clinical trials is changing the treatment landscape for autoimmune diseases including systemic lupus erythematosus. The use of combination therapy and the trend toward lower doses of corticosteroids for LN management are also part of this transformation. The KDOQI work group reviewed the KDIGO guideline statements and practice points and provides perspectives for implementation within the context of clinical practice in the United States. This commentary is the product of the KDOQI work group and presents the recommendations and practice points from the KDIGO guideline, followed by commentary and brief notes on clinical utility, implementation, and challenges.
Since the 1960s, glucocorticoids have been central to induction and maintenance of immunosuppression in kidney transplantation, but their long-term use is associated with significant toxicity, including post-transplant diabetes mellitus, hypertension, dyslipidemia, osteoporosis, infection, and cardiovascular disease. Advances in immunosuppressive regimens have enabled many transplant centers to reduce or eliminate steroids in selected recipients. Emerging monitoring tools, such as donor-specific antibody surveillance, donor-derived cell-free DNA, and gene-expression profiling, support individualized approaches, particularly in lower-risk patients. This review examines the rationale, evidence, and implementation strategies for steroid minimization and avoidance in kidney transplantation, highlighting current practice patterns, patient selection considerations, ongoing controversies, and future directions toward appropriate use of steroid-sparing regimens as part of personalized immunosuppression.
A certain proportion of patients with Mendelian diseases are overlooked, although substantial technical advances in molecular genetics have been achieved. Massively parallel sequencing (MPS) increasingly identifies genetic variants of unknown significance, which may remain clinically unhelpful. Furthermore, difficult niches in the genome exist, which cannot be solved by standard MPS. In the reported family, autosomal dominant kidney disease leading to renal failure in middle adulthood runs through the maternal and paternal family. Comprehensive genetic analyses and customized functional evaluation solved the genetic etiologies: autosomal dominant polycystic kidney disease (ADPKD-PKD1, maternal) and autosomal dominant tubulointerstitial kidney disease (ADTKD-UMOD, paternal), with the index patient suffering from both diseases. The pathogenic variant in PKD1 (c.2180T>C, p.(Leu727Pro)) was not identified by exome sequencing but was unveiled by traditional long-range amplification protocols and whole genome sequencing. The ease of use of MPS increasingly tempts nonspecialized genetic laboratories to perform broad analyses of numerous diseases, which in specific cases may worsen the quality of investigations, ie, for the relatively frequent ADPKD.
