The Improved Kidney Risk Score in ANCA-Associated Vasculitis for Clinical Practice and Trials.

SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 µ mol/L=0, K1: 250-450 µ mol/L=4, K2: >450 µ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.

Immunosuppressive treatment results in patients with primary IgA nephropathy in Turkiye; the data from TSN-GOLD working group.

BACKGROUND: Immunoglobulin A (IgA) nephropathy (IgAN) treatment consists of maximal supportive care and, for high-risk individuals, immunosuppressive treatment (IST). There are conflicting results regarding IST. Therefore, we aimed to investigate IST results among IgAN patients in Turkiye. METHOD: The data of 1656 IgAN patients in the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases Study Group were analyzed. A total of 408 primary IgAN patients treated with IST (65.4% male, mean age 38.4 ± 12.5 years, follow-up 30 (3-218) months) were included and divided into two groups according to treatment protocols (isolated corticosteroid [CS] 70.6% and combined IST 29.4%). Treatment responses, associated factors were analyzed. RESULTS: Remission (66.7% partial, 33.7% complete) was achieved in 74.7% of patients. Baseline systolic blood pressure, mean arterial pressure, and proteinuria levels were lower in responsives. Remission was achieved at significantly higher rates in the CS group (78% vs. 66.7%, p = 0.016). Partial remission was the prominent remission type. The remission rate was significantly higher among patients with segmental sclerosis compared to those without (60.4% vs. 49%, p = 0.047). In the multivariate analysis, MEST-C S1 (HR 1.43, 95% CI 1.08-1.89, p = 0.013), MEST-C T1 (HR 0.68, 95% CI 0.51-0.91, p = 0.008) and combined IST (HR 0.66, 95% CI 0.49-0.91, p = 0.009) were found to be significant regarding remission. CONCLUSION: CS can significantly improve remission in high-risk Turkish IgAN patients, despite the reliance on non-quantitative endpoints for favorable renal outcomes. Key predictors of remission include baseline proteinuria and specific histological markers. It is crucial to carefully weigh the risks and benefits of immunosuppressive therapy for these patients.

Long-Term Outcomes of Living-Related Kidney Donation for Alport Syndrome Spectrum: A Propensity Score-Matched Analysis.

INTRODUCTION: Data to guide the evaluation of living-related donor candidates for kidney transplant recipients with Alport syndrome (AS) spectrum are limited. We aimed to examine a cohort of living-related donors to recipients with AS and compare their outcomes with a control group to improve understanding of the clinical course and outcomes of living donation in this context. METHODS: Living donors (LDs) of AS recipients and propensity score-matched control LDs without any family history of AS (control group) were followed for major cardiac events, death, post-donation estimated glomerular filtration rate (eGFR), and proteinuria. RESULTS: There were 31 LDs (48.4% male), in whom relationship to AS recipient included mother (45.2%), father (32.3%), sibling (16.1%), grandparent (3.2%), and uncle (3.2%). Long-term outcomes over 10.0 (IQR, 3.0-15.0) years were evaluated in 25 and 25 LDs from study and control groups, respectively. During follow-up, 5 LDs (20.0%) in study group developed major cardiac event (acute coronary ischemia [n = 4] and severe congestive heart failure [n = 1]) after 5.5 (IQR, 4.5-10.3) years, whereas only 2 (8.0%) LDs in control group developed major cardiac events (p = 0.221). New-onset hypertension was higher in study group (56.0%) compared to the control group (16.0%) (p = 0.003). Three donors in study and 2 donors in control group who developed new-onset hypertension died during follow-up (p = 0.297). Major cardiac event rate was significantly higher in donors who developed hypertension after donation (0 vs. 28.0%, p < 0.001). There were no differences between study groups regarding last eGFR and proteinuria levels (p = 0.558 and p = 0.120, respectively). DISCUSSION/CONCLUSION: Although the risk of kidney disease can be minimized by careful donor evaluation, our findings suggest that hypertension risk after the donation is higher than expected in related donors of recipients with AS.

Clinical and pathologic features of primary membranous nephropathy in Turkey: a multicenter study by the Turkish Society of Nephrology Glomerular Diseases Working Group.

BACKGROUND: We aimed to evaluate the features of primary membranous nephropathy (MNP) in Turkish people. METHODS: This is a retrospective analysis of patients with biopsy-proven primary MNP. We obtained the data collected between 2009 and 2019 in the primary glomerulonephritis registry of the Turkish Society of Nephrology Glomerular Diseases Study Group (TSN-GOLD). Patients with a secondary cause for MNP were excluded. Clinical, demographic, laboratory, and histopathological findings were analyzed. RESULTS: A total of 995 patients with primary MNP were included in the analyses. Males constituted the majority (58.8%). The mean age was 48.4 ± 13.9 years. The most common presentation was the presence of nephrotic syndrome (81.7%) and sub nephrotic proteinuria (10.3%). Microscopic hematuria was detected in one-third of patients. The median estimated glomerular filtration rate (eGFR) was 100.6 mL/min/1.73 m2 (IQR, 75.4-116.3), and median proteinuria was 6000 mg/d (IQR, 3656-9457). Serum C3 and C4 complement levels were decreased in 3.7 and 1.7% of patients, respectively. Twenty-four (2.4%) patients had glomerular crescents in their kidney biopsy samples. Basal membrane thickening was detected in 93.8% of cases under light microscopy. Mesangial proliferation and interstitial inflammation were evident in 32.8 and 55.9% of the patients, respectively. The most commonly detected depositions were IgG (93%), C3 complement (68.8%), and kappa and lambda immunoglobulin light chains (70%). Although renal functions were normal at presentation, vascular, interstitial, and glomerular findings were more prominent on biopsy in hypertensive patients. No significant effect of BMI on biopsy findings was observed. CONCLUSIONS: Despite some atypical findings, the main features of primary MNP in Turkey were similar to the published literature. This is the largest MNP study to date conducted in Turkish people.

The Effect of Smoking on Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease Patients with Preserved Renal Function.

BACKGROUND: In autosomal dominant polycystic kidney disease (ADPKD), endothelial dysfunction (ED) is common and occurs much earlier than kidney function impairment. The impact of smoking on ED in ADPKD patients has not been previously studied. The aim of this study was to investigate the potential contribution of smoking habits to ED and subclinical atherosclerosis in these patients. METHODS: This case-control study included 54 ADPKD patients with preserved renal function and 45 healthy control subjects. ED was assessed using ischemia-induced forearm flow-mediated dilatation (FMD). Carotid intima-media thickness (CIMT) was measured from 10 mm proximal to the right common carotid artery. Clinical demographic characteristics and laboratory data were recorded for the patients and control group. Regression analysis was used to determine independent associations of ED and CIMT. RESULTS: FMD was significantly lower in the ADPKD patients (19.5 ± 5.63 vs. 16.56 ± 6.41, p = .018). Compared with nonsmoker ADPKD patients, smoker patients had significantly lower FMD values (18.19 ± 6.52 vs. 13.79 ± 5.27, p = .013). In multiple regression analysis, age (ß = -0.294, 95% CI: -0.392: -1.96, p = .001) for FMD and smoking (ß = 1.328, 95% CI: 0.251, 2.404, p = .017) for CIMT were independent predictors. CONCLUSIONS: Patients with ADPKD had more impaired endothelial function and subclinical atherosclerosis compared with control subjects. Smoking may increase the risk of subclinical atherosclerosis in ADPKD patients.

Morning blood pressure surge in early autosomal dominant polycystic kidney disease and its relation with left ventricular hypertrophy.

INTRODUCTION: The activation of the sympathetic nervous system, which usually leads to a swift surge in blood pressure in the morning hours (MBPS) may be the cause of left ventricular hypertrophy (LVH) and endothelial dysfunction (ED) in early autosomal dominant polycystic kidney disease (ADPKD) patients. We studied the association between MBPS and LVH in ADPKD patients with preserved renal functions. METHODS: Patients with ADPKD with preserved renal functions were enrolled. Prewaking MBPS was calculated using ambulatory blood pressure monitoring. The patients were categorized as MBPS (≥median) and non-MBPS (

Pregnancy and its outcomes in hemodialysis patients in Turkey.

BACKGROUND/AIM: This study aimed to investigate pregnancy frequency and evaluate the factors affecting live births in hemodialysis (HD) patients. MATERIALS AND METHODS: Female HD patients whose pregnancy was retrospectively reported between January 1, 2014, and December 31, 2019. The duration of HD, primary disease, whether the pregnancy resulted in abortion, stillbirth, or live birth, whether the HD duration was prolonged after diagnosing the pregnancy and whether it accompanied preeclampsia were recorded. RESULTS: In this study, we reached 9038 HD female patients? data in the study. A total of 235 pregnancies were detected in 145 patients. The mean age was 35.42 (35 ± 7.4) years. The mean age at first gestation was 30.8 ± 6.5 years. The average birth week was 32 (28 - 36) weeks. 53.8% (no = 78) of the patients had live birth, 51.7% (no = 70) had at least one abortion in the first 20 weeks, and 13.1% (no = 19) had at least one stillbirth after 20 weeks. The rate of patients' increased numbers of dialysis sessions during pregnancy was 71.7%. The abortion rate was 22.4% in those with increased HD sessions, whereas 79.3% in those not increased HD sessions (p < 0.001). Live birth frequency was 67.2% in the increased HD sessions group and 3.4% in those who did not differ in HD sessions (p < 0.001). CONCLUSION: For the first time, we reported pregnancy outcomes in HD female patients, covering all regions of Turkey. It has been observed that; increasing the number of HD sessions in dialysis patients will decrease fetal and maternal complications and increase live birth rates.

Association of monocyte to HDL cholesterol level with contrast induced nephropathy in STEMI patients treated with primary PCI.

BACKGROUND: Contrast induced nephropathy (CIN) has been proven to be a clinical condition related to adverse cardiovascular outcomes. In recent studies, the monocyte to high density lipoprotein ratio (MHR) has been postulated as a novel parameter associated with adverse renal and cardiovascular outcomes. In this study we investigated the association of MHR with CIN in ST-segment elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). METHODS: Consecutive STEMI patients treated with primary PCI were prospectively recruited. Subjects were categorized into two groups; as patients who developed CIN (CIN+) and patients who did not develop CIN (CIN-) during hospitalization. CIN was defined as either a 25% increase in serum creatinine from baseline or 44.20 µmol/L increase in absolute value, within 72 h of intravenous contrast administration. RESULTS: A total number of 209 patients were included in the study. Thirty-two patients developed CIN (15.3%). In the CIN (+) patients, monocytes were higher [1.02 (0.83-1.39) vs. 0.69 (0.53-0.90) 109/L, p<0.01] and HDL cholesterol levels were lower [0.88 (0.78-1.01) vs. 0.98 (0.88-1.14) mmol/L, p<0.01]. In addition, MHR was significantly higher in the CIN (+) group [1.16 (0.89-2.16) vs. 0.72 (0.53-0.95) 109/mmol, p<0.01]. In multivariate logistic regression analysis, MHR, Mehran score, AGEF score and CV/eGFR were independently correlated with CIN. CONCLUSIONS: Higher MHR levels may predict CIN development after primary PCI in STEMI patients.

Colchicine in Renal Medicine: New Virtues of an Ancient Friend.

Colchicine is a plant-derived alkaloid that disrupts the cell microtubule system and accumulates in neutrophils, inhibiting neutrophil adhesion and recruitment. Colchicine has been used extensively in the prevention and treatment of gouty arthritis attacks, familial Mediterranean fever attacks and resultant AA amyloidosis, and recurrent pericarditis. Colchicine also disrupts the intracellular traffic of additional inflammatory and fibrosis mediators. Renal fibrosis is the final common pathway of chronic renal disease. Colchicine had anti-fibrotic effects in experimental diabetic nephropathy, renal mass reduction, and cyclosporine nephrotoxicity among others and is undergoing clinical trials for non-diabetic metabolic syndrome and diabetic nephropathy. In this review, we summarize the anti-inflammatory and anti-fibrotic properties of colchicine in experimental and clinical studies in renal diseases or other fibrotic disease processes with renal consequences. We also discuss the potential future uses of colchicine in renal medicine and challenges faced with its use in patients with impaired kidney function.

Attitudes of neurology specialists toward older adults.

OBJECTIVE: Attitude of healthcare providers toward older people is very important in the aging world. Neurologists contact older adults very frequently. We aimed to investigate the attitudes of neurologists toward older adults. MEASUREMENTS: We recorded participants age; sex; duration of clinical practice in neurology; existence of older adult relatives; and history of geriatrics education, nursing home visits, older adult patient density in their clinical practice, and participation in voluntary public activities. UCLA Geriatrics Attitude Scale was used to evaluate participants' attitudes. RESULTS: A total of 100 neurologists participated in this study. Seventy-seven percent had positive, 3 % had neutral, and 20 % had negative attitudes. Twenty-seven percent of the participants had history of geriatrics education, and these participants tended to have a higher rate of positive attitudes. Neurologists with positive attitudes tended to be older than those with negative attitudes. Participants with history of living with older adult relatives had lower rates of positive attitudes. The most common diagnoses of the patients the participants encountered were stroke and dementia. Independent factors associated with positive attitudes were history of geriatrics education and older age. History of living with older relatives tended to have a negative effect. Most of the negative items of the attitude scale were associated with the natural course and behavior of the common diseases in neurology practice. CONCLUSIONS: Generalization of geriatrics education may translate into a better understanding and improved care for older patients. Development of instruments and implementation of qualitative studies to assess attitudes of neurologists toward older adults are needed.

Restless-legs syndrome and insomnia in hemodialysis patients.

AIM/BACKGROUND: Restless legs syndrome (RLS) is a common neurological movement disorder which is commonly seen in hemodialysis (HD) patients. Insomnia, depression, and anxiety disorders frequently show concurrence. In this study, we aimed to investigate RLS and insomnia prevalence and related factors in HD patients. SUBJECTS AND METHODS: Patients who were under HD treatment and healthy controls with similar mean age, sex ratio, and hypertension and diabetes mellitus frequency were included in this study. Depression, insomnia, and daytime sleepiness assessments were performed by using Beck Depression Inventory, Insomnia Severity Index, and Epworth Sleepiness Scale. The diagnosis of RLS was made using the International RLS Study Group consensus criteria. RESULTS: About 156 HD patients and 35 controls were enrolled. The mean age was 50.6 in the HD group and 49.7 in the control group. Female sex was 43.9% in the HD group and 57.1% in the control group. RLS was significantly more frequent in HD patients compared with controls. The rate of sub-threshold insomnia and insomnia with moderate severity was higher in HD patients. While insomnia severity score and diabetes mellitus were significantly associated with the presence of RLS, depression, RLS, older age, and being under HD treatment were independently associated with insomnia severity. CONCLUSIONS: HD patients commonly have RLS and insomnia. Insomnia and diabetes mellitus seem to be major factors underlying RLS in HD patients. Furthermore, depression and RLS seem to be closely related to insomnia in these patients. Treatment of depression, insomnia, and RLS may be beneficial to improve quality of life in HD patients.

Analysis of liver function test abnormalities in kidney transplant recipients: 7 year experience.

OBJECTIVE: Immunosuppressive drugs, antimicrobial agents and infectious complications may cause liver function test abnormalities (LFTA) in kidney transplant recipients (KTR). The objectives of this study were to identify the outcome of (LFTA). To identify the risk factors affecting development and severity of hepatotoxicity in KTR. METHODS: We retrospectively evaluated the medical records of KTR. Hepatotoxicity attacks were defined as impairment in liver function tests that was responsive to drug dose reduction or discontinuation, or treatment of specific causes such as infectious complications. RESULTS: One hundred-fifty-six episodes of hepatotoxicity occurred in 107 patients in 281 KTR, with an incidence of 38%. Patients with hepatotoxicity episodes had a high total mortality rate, higher incidence of positive pre-transplant cytomegalovirus (CMV) IgM test, higher creatinine values during the first month post-transplant, underwent additional acute rejection episodes, and received fewer cyclosporin A based ID. Only positive CMV IgM testing was identified as a significant independent risk factor for hepatotoxicity in our multiple analysis. Mycophenolatemofetil (MMF) related hepatotoxicity was the most common cause of drug related LFTA. CONCLUSIONS: Patients with LFTA can have significant complications. Pre-transplant positive CMV IgM tests predispose transplant recipients to the development of LFTA during the post-transplant period. MMF can be a serious hepatotoxic drug.

Urea to creatinine ratio: a forgotten marker of poor nutritional state in patients undergoing hemodialysis treatment.

BACKGROUND: Malnutrition is common in subjects undergoing hemodialysis and is associated with increased morbidity and mortality. Studies investigating factors associated with malnutrition and effect of various interventions to treat these patients are needed. We aimed to screen older and young patients undergoing chronic hemodialysis, for malnutrition, and seek its association with clinical factors including anxiety and depression and laboratory variables including urea/creatinine ratio (UCR). METHODS: Duration of hemodialysis treatment, medications taken, anthropometric measurements and routine laboratory results were recorded. Mini nutritional assessment and Beck anxiety and Beck depression inventories were applied. Study variables between subjects with malnutrition, malnutrition risk and normal nutritional states were compared. Older and younger patients were also compared regarding malnutrition and laboratory results. Linear regression analysis was performed to seek independent factors associated with malnutrition score. RESULTS: Clinical and laboratory data except for UCR were found to be similar among young and older patients. UCR increased, while albumin, body mass index and weight circumference decreased along with worse nutritional state. Low albumin level, body mass index and UCR and higher hemoglobin level and depression score were independent factors associated with malnutrition. CONCLUSION: In addition to routinely used markers of malnutrition UCR may provide additional information regarding malnutrition in this population.

Invasive Fungal Infections in Renal Transplant Recipients: Epidemiology and Risk Factors.

BACKGROUND: Invasive fungal infections are a major cause of morbidity and mortality among renal transplant recipients. OBJECTIVES: The aim of this study was to investigate the frequency and risk factors for fungal infections in renal transplant recipients. METHODS: We retrospectively evaluated all kidney transplant recipients at our center from December 1988 to June 2010 for the epidemiology, spectrum, risk factors, and mortality of invasive fungal infections. RESULTS: In 32 patients (10.30 %), at least one fungal infection developed after the transplantation. The most common pathogens causing fungal infections in our patients were Candida spp. and Aspergillus spp. The independent risk factors associated with invasive fungal infection episodes were antibiotic treatment within the last 3 months (OR 15.88, 95 % CI 3.90-64.73, p < 0.001), cytomegalovirus infection (OR 18.54, 95 % CI 9.01-38.17, p < 0.001), and the presence of diabetes mellitus (OR 6.01, 95 % CI 2.95-12.25, p < 0.001). Mortality was significantly higher among patients with fungal infections than among other patients (53.10 and 17.80 %, respectively; p < 0.001). CONCLUSIONS: It is difficult to diagnose and treat fungal infections early, and it can be useful to determine independent risk factors in order to identify and treat high-risk patients.

Modified histopathological classification with age-related glomerulosclerosis for predicting kidney survival in ANCA-associated glomerulonephritis.

BACKGROUND: The histopathological classification of ANCA-GN divides patients into four groups based on signs of glomerular injury. However, this classification did not consider age-related glomerulosclerosis. In this study, we aimed to compare the prediction of renal survival between Berden's ANCA-GN histopathological classification and ANCA-GN histopathological classification modified with age-related glomerulosclerosis. METHODS: Between January 2004 and December 2019, 65 patients diagnosed with ANCA-GN were enrolled. Demographic, laboratory, and histopathologic findings were retrospectively analyzed. Renal survival analyses were compared according to classical and modified ANCA-GN histopathological classifications. Multivariate Cox regression analysis for the factors affecting renal survival was performed. RESULTS: In Berden's ANCA-GN histopathological classification, 15 patients were in the focal group, 21 in the crescentic, 21 in the sclerotic, and 8 in the mixed group. The ANCA-GN histopathological classification model generated statistically significant predictions for renal survival (p = 0.022). When the histopathological classification was modified with age-related glomerulosclerosis, eight of the nine patients previously classified in the sclerotic group were classified in the mixed and one in the crescentic groups. Modification of histopathological classification with age-related glomerulosclerosis increases the statistical significance in renal survival analysis (p = 0.009). The multivariate Cox regression analysis showed that the disease-related global sclerotic glomeruli percentage and serum creatinine level were significant independent factors. CONCLUSION: Modification of Berden's ANCA-GN histopathological classification model with age-related glomerulosclerosis may increase the statistical significance of the histopathological classification model.

Relationship between disease awareness and severity of kidney disease in autosomal dominant polycystic kidney disease patients.

INTRODUCTION: Polycystic kidney disease (PKD) is responsible for 5%-10% of end-stage renal disease. We examined the relationship between renal and extrarenal findings, disease severity, and the level of consciousness of PKD patients. METHODS: Patients were asked to answer the questionnaire about PKD. Disease severity was determined according to estimated glomerular filtration rate, and disease awareness was assessed by adapting the Disease Perception Scale to PKD. Awareness of patients was evaluated comparatively with chronic kidney disease stage, age, region, and symptoms. RESULTS: One out of five patients does not know that this disease is inherited. Mean awareness scores of the patients decreased significantly with increasing age. Awareness scores were significantly higher in patients with flank pain, hematuria, and urinary tract stones. CONCLUSION: Although PKD is the most common hereditary kidney disease, the rate of patients' knowledge on this subject is low. Increased awareness might lead to better treatment in those patients.

Propensity score-matched analysis of long-term outcomes for living kidney donation in alternative complement pathway diseases: a pilot study.

BACKGROUND: Atypical hemolytic syndrome (aHUS) and C3 glomerulopathy (C3G) are complement-mediated rare diseases with excessive activation of the alternative pathway. Data to guide the evaluation of living-donor candidates for aHUS and C3G are very limited. The outcomes of living donors to recipients with aHUS and C3G (Complement disease-living donor group) were compared with a control group to improve our understanding of the clinical course and outcomes of living donation in this context. METHODS: Complement disease-living donor group [n = 28; aHUS(53.6%), C3G(46.4%)] and propensity score-matched control-living donor group (n = 28) were retrospectively identified from 4 centers (2003-2021) and followed for major cardiac events (MACE), de novo hypertension, thrombotic microangiopathy (TMA), cancer, death, estimated glomerular filtration rate (eGFR) and proteinuria after donation. RESULTS: None of the donors for recipients with complement-related kidney diseases experienced MACE or TMA whereas two donors in the control group developed MACE (7.1%) after 8 (IQR, 2.6-12.8) years (p = 0.15). New-onset hypertension was similar between complement disease and control donor groups (21.4% vs 25%, respectively, p = 0.75). There were no differences between study groups regarding last eGFR and proteinuria levels (p = 0.11 and p = 0.70, respectively). One related donor for a recipient with complement-related kidney disease developed gastric cancer and another related donor developed a brain tumor and died in the 4th year after donation (2, 7.1% vs none, p = 0.15). No recipient had donor-specific human leukocyte antigen antibodies at the time of transplantation. Median follow-up period of transplant recipients was 5 years (IQR, 3-7). Eleven (39.3%) recipients [aHUS (n = 3) and C3G (n = 8)] lost their allografts during the follow-up period. Causes of allograft loss were chronic antibody-mediated rejection in 6 recipients and recurrence of C3G in 5. Last serum creatinine and last eGFR of the remaining patients on follow up were 1.03 ± 038 mg/dL and 73.2 ± 19.9 m/min/1.73 m2 for aHUS patients and 1.30 ± 0.23 mg/dL and 56.4 ± 5.5 m/min/1.73 m2 for C3G patients. CONCLUSION: The present study highlights the importance and complexity of living related-donor kidney transplant for patients with complement-related kidney disorders and motivates the need for further research to determine the optimal risk-assessment for living donor candidates to recipients with aHUS and C3G.

Skeletal muscle energetics in patients with moderate to advanced kidney disease.

Sarcopenia, defined as decrease in muscle function and mass, is common in patients with moderate to advanced chronic kidney disease (CKD) and is associated with poor clinical outcomes. Muscle mitochondrial dysfunction is proposed as one of the mechanisms underlying sarcopenia. Patients with moderate to advanced CKD have decreased muscle mitochondrial content and oxidative capacity along with suppressed activity of various mitochondrial enzymes such as mitochondrial electron transport chain complexes and pyruvate dehydrogenase, leading to impaired energy production. Other mitochondrial abnormalities found in this population include defective beta-oxidation of fatty acids and mitochondrial DNA mutations. These changes are noticeable from the early stages of CKD and correlate with severity of the disease. Damage induced by uremic toxins, oxidative stress, and systemic inflammation has been implicated in the development of mitochondrial dysfunction in CKD patients. Given that mitochondrial function is an important determinant of physical activity and performance, its modulation is a potential therapeutic target for sarcopenia in patients with kidney disease. Coenzyme Q, nicotinamide, and cardiolipin-targeted peptides have been tested as therapeutic interventions in early studies. Aerobic exercise, a well-established strategy to improve muscle function and mass in healthy adults, is not as effective in patients with advanced kidney disease. This might be due to reduced expression or impaired activation of peroxisome proliferator-activated receptor-gamma coactivator 1α, the master regulator of mitochondrial biogenesis. Further studies are needed to broaden our understanding of the pathogenesis of mitochondrial dysfunction and to develop mitochondrial-targeted therapies for prevention and treatment of sarcopenia in patients with CKD.

Sodium-glucose cotransporter inhibition in polycystic kidney disease: fact or fiction.

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent hereditary kidney disease. Recent evidence suggests that the pathogenesis of ADPKD is a complex web of abnormal cellular processes including altered cell signaling, disordered cell metabolism, impaired autophagy, increased apoptosis, mitochondrial dysfunction and chronic inflammation. Sodium-glucose cotransporter (SGLT) inhibitors (SGLTi) reduce body weight, blood pressure and blood glucose levels, have kidney and cardiovascular protective activity, and have been reported to decrease inflammation, increase autophagy and improve mitochondrial dysfunction. We now review results from preclinical studies on SGLTi for ADPKD identified through a systematic search of the MEDLINE, Cochrane Library, Embase and PubMed databases. Potential underlying mechanisms for the conflicting results reported as well as implications for clinical translation are discussed, as ADPKD patients were excluded from clinical trials exploring kidney protection by SGLT2 inhibitors (SGLT2i). However, they were not excluded from cardiovascular safety trials or trials for cardiovascular conditions. A post-hoc analysis of the kidney function trajectories and safety of SGLT2i in ADPKD patients enrolled in such trials may provide additional information. In conclusion, SGLT2i are cardio- and nephroprotective in diverse clinical situations. Currently, it is unclear whether ADPKD patients may benefit from SGLT2i in terms of kidney function preservation, and their safety in this population remains unexplored. We propose a roadmap to address this unmet clinical need.