Nephrology Dialysis Transplantation最新文献

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and finerenone each improve kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD). This study compares the association between combined therapy versus monotherapy with SGLT2i or finerenone and the kidney, cardiovascular and mortality outcomes in CKD patients.

Methods: This retrospective cohort study included adults ≥18 years with CKD between 9 July 2021, and 30 November 2023 from multiple centers in the USA, utilizing the TriNetX database. Exposures included treatment with finerenone, SGLT2i or a combination of both. The primary outcome was major adverse kidney events (MAKE). Secondary outcomes included all-cause mortality, major adverse cardiac events (MACE) and end-stage renal disease (ESRD).

Results: A total of 853 patients were included in the combined group [mean (±standard deviation) age, 66.7 ± 11.4 years; 34.9% female], 942 in the finerenone group (mean age, 68.2 ± 11.4 years; 45.8% female) and 45 948 in the SGLT2i group (mean age, 70.2 ± 11.8 years; 41.4% female). After matching, the combined group had less MAKE compared with finerenone monotherapy [adjusted hazard ratio (aHR) 0.20; 95% confidence interval (CI) 0.09-0.45] or SGLT2i monotherapy (aHR 0.44; 95% CI 0.22-0.89). The hazards of all-cause mortality and ESRD were also lower in the combined group compared with either finerenone or SGLT2i alone, while hazard of MACE was similar between the combined and monotherapy groups. The combined group had higher risk of hyperkalemia compared with SGLT2i monotherapy (aHR = 1.36; 95% CI 1.08-1.71).

Conclusion: Combined therapy with finerenone and SGLT2i is associated with less MAKE and all-cause mortality in CKD patients compared with monotherapy. However, the risk of hyperkalemia with finerenone warrants caution.

Background: The treatment strategy for non-immunoglobulin light chain (AL) amyloidosis monoclonal gammopathy of renal significance (MGRS) remains unstandardized. Autologous hematopoietic stem cell transplantation (ASCT) has shown favorable results in a limited number of studies.

Methods: This single-center, retrospective case-control study included non-AL amyloidosis MGRS patients diagnosed between February 2012 and July 2024; these patients were divided into the ASCT group and non-ASCT group. Baseline characteristics, ASCT characteristics and complications, treatment responses, survival outcomes, and risk factors for progression-free survival (PFS) were analyzed.

Results: A total of 53 patients with non-AL amyloidosis MGRS were enrolled in this study, comprising 23 patients who received ASCT and 30 patients who did not receive ASCT. The baseline characteristics were comparable between the ASCT and non-ASCT groups, with exceptions of serum albumin and C3 levels. The median overall survival (OS) and renal survival were not reached in either group. The median PFS was significantly longer in the ASCT group compared to the non-ASCT group (58.4 vs 16.4 months, P = .004). The overall response rate (ORR) and deep response rates of the ASCT group were higher than those of the non-ASCT group, both in hematological and renal responses. In the ASCT group, 18 patients (78.3%) achieved a hematological very good partial response (VGPR) or better, and 21 patients (91.3%) achieved a renal partial response or better after transplantation. Moreover, the ASCT group exhibited higher long-term cumulative incidences of OS and renal survival. The toxicity of ASCT was manageable, and no transplantation-related deaths occurred. There was no statistically significant difference in the median PFS between monoclonal immunoglobulin deposition disease and light chain proximal tubulopathy (P = .539). High serum albumin level at diagnosis, and hematological response ≥VGPR after ASCT were protective factors of PFS.

Conclusions: This study confirmed that ASCT was an effective and safe treatment for patients with non-AL amyloidosis MGRS, thereby offering long-term hematological remission and survival benefits.

Background: This study aimed to evaluate the efficacy and safety of telitacicept for the treatment of lupus nephritis (LN) in real-world clinical practice.

Methods: Adult patients with LN receiving additional telitacicept at 80/160 mg once per week were recruited, while patients receiving only standard therapy were included as the control group using a 1:1 propensity score-matching approach. The primary outcomes were the proportions of patients achieving complete renal response (CRR) and primary efficacy renal response (PERR).

Results: Forty-four patients in both the control and telitacicept groups were enrolled, with median follow-up periods of 10.78 ± 3.37 and 10.5 ± 3.78 months, respectively. Compared with the control group, a significant improvement was observed in the proportion of patients achieving CRR (11.36% vs 29.55%, P = .034) and PERR (45.45% vs 68.18%, P = .031) in the telitacicept group at the last visit. Median proteinuria was reduced by 0.97 g/day (63.82%) from baseline in the telitacicept group, compared with a reduction of 0.31 g/day (25.31%) in the control group. Additionally, the telitacicept group showed notable treatment responses in the median SLE Disease Activity Index-2000 score, Physician's Global Assessment score and glucocorticoid dose reduction. Subgroup analysis revealed that telitacicept exhibited a more prominent therapeutic effect in patients with type V LN and those with proteinuria exceeding 3 g/day. Telitacicept was well tolerated, and the incidence of adverse events was similar between the two groups.

Conclusions: LN patients receiving additional telitacicept treatment demonstrated better disease remission, particularly in those with type V LN and proteinuria ≥3 g/day, with a favorable safety profile in real-world clinical practice.

Kidney disease is a global health priority affecting >850 million people worldwide. This number is projected to increase over the coming decades given the increasing prevalence of diabetes, hypertension and obesity and the aging population. Chronic kidney disease (CKD) can reduce both life expectancy and quality of life and is intricately linked with cardiac and metabolic health-the cardiovascular-kidney-metabolic multimorbidity syndrome. With early recognition of risk, CKD can be prevented and with timely case finding, early diagnosis and early intervention, its progression can be halted or slowed. The European Renal Association has established the Strong Kidneys Task Force, with the main purpose of creating awareness about the importance of kidney health for individual and population health. In collaboration with the European Kidney Health Alliance and the European Kidney Patients Federation, the ABCDE campaign will empower communities and individuals to remind their healthcare providers to assess their risk of kidney disease. ABCDE asks five simple questions about health status that only the healthcare system can provide: A) Do I have Albumin in my urine? B) What is my Blood pressure? C) What is my Cholesterol? D) Do I have Diabetes? E) What is my current kidney function (Estimated glomerular filtration rate)? This advocacy text aims to inform individuals, communities and front line healthcare workers that capturing the risk of kidney, cardiac and metabolic health is simple, makes sense, is logical and will save lives. Although making meaningful change will take time and involve major personal and societal changes, the first step really is as easy as ABCDE!

Background: Drug-induced acute interstitial nephritis (DI-AIN) represents a common cause of acute kidney injury. Early withdrawal of the culprit drug and corticosteroid therapy remains the mainstay of treatment. This study aimed to develop and validate a predictive nomogram to assess the probability of recovery of kidney function at 6 months after treatment.

Methods: A multicenter, retrospective, observational study was conducted in 13 nephrology departments. Patients with biopsy proven DI-AIN treated with corticosteroids between 1996 and 2023 were included. The dataset was randomly divided into training (n = 164) and validation (n = 60) sets. Least absolute shrinkage and selection operator regression was used to screen the main predictors of complete (creatinine increase <25% of the last value before DI-AIN) or no recovery of kidney function (serum creatinine ≥75% or need for dialysis).

Results: The study group comprised 224 patients with DI-AIN: 51 (31%) in the training group and 19 (32%) in the validation set achieved complete recovery at 6 months. Conversely, 33 (20%) and 8 (13%) patients in the two sets showed no recovery at 6 months. Clinical characteristics were well balanced between training and validation sets. The selected variables were age (under/above 65 years), gender, degree of interstitial fibrosis and time to corticosteroid initiation (under/above 7 days). Based on a multivariable logistic regression model, a nomogram was developed. The area under the curve of the nomogram was 0.79 (95% confidence interval 0.71-0.88), indicating good discriminative power. Bootstrap self-sampling was performed 1000 times for validation of the model. A calibration plot revealed that the predicted outcomes aligned well with the observations. Decision curve analysis suggested that the model had clinical benefit.

Conclusions: We developed and validated a nomogram to predict kidney recovery at 6 months in DI-AIN patients treated with corticosteroids. This tool helps clinicians estimate prognosis and optimize corticosteroid therapy's intensity and duration for better treatment outcomes.

Background: Primary focal segmental glomerulosclerosis (FSGS) is characterized by podocyte injury and treatment-resistant nephrotic syndrome. Recurrence of the original disease after kidney transplantation (rFSGS) occurs in 10%-50% of patients. Unidentified circulating permeability factors (CPF) are likely involved in FSGS pathogenesis. We hypothesized that donor podocyte susceptibility to CPF is also relevant. We developed a personalized model for (r)FSGS using induced pluripotent stem cell (iPSC)-derived podocytes from patients and kidney donors.

Methods: Five patients and their respective living kidney donors were included. Three patients had developed rFSGS, and two patients manifested no symptoms of rFSGS. One patient (P5) had heterozygous mutations in NPHS2. Peripheral blood mononuclear cells were reprogrammed to iPSC, and differentiated to podocytes. iPSC-derived podocytes from either patients or donors were exposed to presumed CPF-containing plasma/serum of corresponding patients. Three assays to detect podocyte injury were performed: (i) reactive oxygen species formation, (ii) cellular granularity induction, and (iii) quantitative assessment of F-actin redistribution (FAR), a new quantitative method. Crossmatch experiments with donor iPSC-derived podocytes and patients samples assessed individual susceptibility to CPF-induced injury.

Results: Successful podocyte differentiation was confirmed by morphology and protein expression. Only FAR differentiated consistently between patient and healthy donor samples. All pre-transplant patient samples except P5 caused significant FAR in corresponding patient podocytes. Significant FAR was observed in donor podocytes exposed to corresponding patient samples in the setting of rFSGS, and not in donor podocytes exposed to samples of patients who did not develop rFSGS. Effects of FSGS patient samples on non-corresponding donor podocytes were variable.

Conclusions: In vitro assays using iPSC-derived donor podocytes may allow individualized assessment of rFSGS. Prospective studies in a larger cohort are required to validate our findings.

Background and hypothesis: The only therapy to ameliorate disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) is tolvaptan, a vasopressin V2 receptor antagonist. Real-life data on long-term tolvaptan treatment are sparse and limited by restricted follow-up, small patient groups or lack of a control group. We studied the long-term effect of tolvaptan on kidney function and kidney growth in real-life patients and controls. Moreover, we investigated determinants of long-term treatment efficacy.

Methods: Data from the prospective DIPAK cohort and retrospective OBSERVA cohort were pooled. estimated glomerular filtration rate (eGFR) was measured at least yearly and total kidney volume (TKV) at least every 3 years. Treatment effects from the start to 6 weeks after initiation of tolvaptan were analyzed as "acute slope." After this, endpoints were analyzed as "chronic slope." As a control group, we included all patients who were not treated with tolvaptan, assessing change in endpoints before and during theoretical treatment (based on the average time of tolvaptan initiation in tolvaptan-treated patients).

Results: A total of 615 patients (48 ± 12 years, 58.2% female) were included in the full analysis, of which 105 (17.1%) were treated with tolvaptan. The average duration of treatment was 6.1 ± 4.7 years (range 0.8 to 15.9). After matching, two groups of 92 patients remained for matched analysis. In this analysis, tolvaptan reduced eGFR decline during chronic slope by 14.0% (-4.36 to -3.75 mL/min/1.73 m2/year, P = .03), versus a decrease of 1.0% (-4.16 to -4.12 mL/min/1.73 m2/year, P = .9) in the control group. Long-term TKV growth did not significantly change during tolvaptan treatment (5.05 to 5.59%/year P = .6). In subgroup analyses, patients with a higher mean osmolar intake had a larger treatment effect of tolvaptan.

Conclusion: In this study, with real-life patient data, long-term follow-up and a well-matched control group, we found that tolvaptan attenuated long-term kidney function decline but seemed not to influence kidney growth.