Nephrology Dialysis Transplantation最新文献

Combination therapy, involving the use of multiple medications together, is becoming a new standard of care for chronic kidney disease (CKD). For people with CKD, combination therapy offers the promise of preventing kidney failure and reducing the risk of heart problems. This approach is appealing because different drugs target distinct mechanisms involved in CKD progression. For instance, some target immune responses, others reduce kidney inflammation and scarring, while others improve blood pressure within the kidneys. Data from large clinical trials suggest that each treatment works effectively on its own, regardless of other medications people are taking. Combining therapies can also reduce the risk of side effects of individual medications. This review highlights the evidence for combination therapy in CKD, explores how to improve its use, and discusses how future studies may answer remaining questions.

Abstract: A range of therapies now exists to reduce the risk of kidney failure and cardiovascular events in people with type 2 diabetes, including renin-angiotensin system blockade, sodium-glucose cotransporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists. With multiple clinical trials underway, it is likely that at least some of these therapies-as well as additional agents such as endothelin receptor antagonists-will further demonstrate kidney-protective effects in people with CKD who do not have diabetes in the near future. For conditions such as IgA nephropathy, several therapies have recently been approved or are being evaluated in late phase trials. Thus combination therapy is emerging as a new standard for diabetic and non-diabetic chronic kidney disease (CKD). This approach is supported by randomized data suggesting that each therapeutic class offers independent and additive benefits in diabetic kidney disease, regardless of background therapy. Notably, the reduction in hyperkalaemia and fluid retention with SGLT2 inhibitors may enhance the tolerability and safety of other treatments. In this review, we present the rationale for combination therapy with evidence-based kidney therapies in diabetic and non-diabetic CKD. We also summarize randomized evidence supporting a multi-medicine approach, address safety considerations, review ongoing trials, and propose frameworks for implementing treatments aligned with patient risk to optimize person-centred care and reduce long-term risks of kidney failure and related complications.

Background: Renal red blood cell casts (RBCC) are common in IgA nephropathy (IgAN), but their role in kidney disease progression of patients with IgAN remains unclear.

Methods: 1425 patients in Peking University First Hospital IgAN (PKU-IgAN) cohort and 279 patients in TESTING trial were enrolled to test the association between RBCC and kidney outcome. RBCC was defined as positive (+) when at least one cast was identified within the renal tubules by light microscopy. Kidney endpoint was the composite of the first occurrence of a sustained 30% decrease in estimated glomerular filtration rate or end stage kidney disease or death due to kidney disease. Cox regression analysis was used.

Results: In PKU-IgAN, 529 patients (37%) had RBCC; in TESTING trial, 78 patients (28%) had RBCC. Patients with RBCC had more crescentic lesions, and less segmental sclerosis compared with patients without RBCC. In PKU-IgAN, after a median follow-up of 54 months, 119 patients (22%) with RBCC and 260 patients (29%) without RBCC reached the composite kidney endpoint (P=0.009). In multivariable analysis, RBCC was independently associated with composite kidney endpoint (HR 0.79; 95%CI 0.63 - 0.99; P=0.038). RBCC and immunosuppressive therapy (IST) had an interaction (P=0.001). RBCC was independently associated with composite kidney endpoint in patients who received IST (HR 0.56; 95%CI 0.40 - 0.77; P<0.001). In TESTING trial, after a median follow-up of 57 months, 26 patients (33%) with RBCC and 96 patients (48%) without RBCC reached the composite kidney endpoint (P=0.041). In univariate analysis, RBCC was associated with composite kidney endpoint (HR 0.64; 95%CI 0.42 - 0.99; P=0.047).

Conclusion: Renal RBCC was frequent in IgAN and was associated with a higher incidence of acute active lesions and better renal prognosis, especially in those who received IST, warranting particular attention.

People with chronic kidney disease (CKD) are at a high risk of heart disease and end-stage kidney disease. This review describes how new medications, such as glucagon-like peptide-1 receptor agonists (GLP1RA), aldosterone synthase inhibitors (ASi), soluble guanylate cyclase (sGC) and endothelin receptor antagonists (ERA), can lower heart-kidney risk in people with CKD. GLP1RA are already recommended for managing blood sugar in people with CKD and type 2 diabetes and have been shown to lower the risk of developing end-stage kidney disease. GLP1RA will likely soon be included in clinical guidelines, but further research is needed to understand how these medications protect the kidneys. ASi are another new medication that lower the protein found in urine. Larger trials are being done to see how well these medications work in slowing CKD. Lastly, both sGC agonists and ERAs have been shown to relax blood vessels to improve blood flow in the kidney, and reduce the amount of protein found in urine, both of which are critical to protecting kidneys. Larger clinical trials are being done to see if these medications prevent CKD from getting worse. In summary, this review describes the new and promising treatments for CKD. These therapies hold the potential to slow kidney disease and improve the wellbeing of patients. Further research of these new treatments is important for improving CKD care.

Abstract: Despite recent advancements in the treatment of chronic kidney disease (CKD), identifying novel therapies beyond guideline-directed therapies that reduce residual cardiorenal risk remains imperative. In this review, we highlight the clinical evidence supporting emerging therapies for CKD, including glucagon-like peptide-1 receptor agonists (GLP1RA) and other incretin-based therapies, aldosterone synthase inhibitors (ASI), endothelin receptor antagonists (ERA), soluble guanylate cyclase (sGC) agonists and anti-inflammatory drugs. Long-acting GLP1RA are already recommended for glycemic control in patients with CKD and type 2 diabetes and the large, dedicated kidney outcome trial FLOW was recently stopped early for efficacy. Emerging clinical trial evidence supports the concept that ASI also provide additional benefit on top of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, which remain a cornerstone of CKD treatment. Next, we consider the use of sGC agonists, which target nitric oxide bioavailability and thereby reduce albuminuria. Finally, we explore the therapeutic potential of ERA, which act through hemodynamic and anti-fibrotic mechanisms, thereby addressing a common final pathway in the development of CKD. Accordingly, our review highlights the changing therapeutic landscape for CKD with promising agents to further prevent the progression of kidney disease.

Background: End-stage kidney disease (ESKD) has an elevated risk of osteoporotic fractures in relation to mineral and bone disorder (MBD) as well as conventional risks of osteoporosis. We investigated the association between oral phosphate binders, the mainstay of MBD treatment, and osteoporotic fracture in dialysis patients.

Methods: We obtained data from the National Health Insurance database for incident dialysis patients without a history of osteoporotic fractures. Participants were categorized into four groups based on their initial 1-year prescription profiles: calcium-based phosphate binder (CBPB), non-calcium-based phosphate binder (NCBPB), both CBPB and NCBPB (mixed), and non-phosphate binder (non-user) groups. The primary outcome was the occurrence of new-onset osteoporotic fractures after 1 year of dialysis. Secondary outcomes included cardiovascular events and mortality.

Results: Out of 69 368 incident dialysis patients, 22 326, 5020, 2853 and 39 169 were included in the CBPB, NCBPB, mixed and non-user groups, respectively. The overall risk of osteoporotic fractures was lower in patients taking any phosphate binders compared with non-users. Specifically, only the CBPB group showed a reduced risk of vertebral [adjusted hazard ratio (aHR) 0.83 (0.76-0.92)], hip [aHR 0.81 (0.74-0.89)] and distal radius [aHR 0.88 (0.78-0.99)] fractures compared with non-users. This relationship presented in a time-dependent manner with fracture risk reduction in patients taking CBPB for 3-6 months [aHR 0.9 (0.83-0.99)] and ≥6 months [aHR 0.83 (0.78-0.89)], compared with those using CBPB for <3 months. Additionally, only the CBPB group had a lower risk of MACE, cardiac arrest and ventricular arrhythmia than non-users. All phosphorus binder groups showed a reduced mortality risk compared with non-users.

Conclusions: Our findings indicate that the using phosphate binders in ESKD patients is lowers the risk of osteoporotic fractures. Notably, those taking CBPB had a reduced risk without increasing cardiovascular events or mortality compared with non-users.

Background: Congenital anomalies of the kidney and urinary tract (CAKUT), often discovered in utero, cover a wide spectrum of outcomes ranging from normal postnatal kidney function to foetal death. The current ultrasound workup does not allow for an accurate assessment of the outcome. The present study aimed to significantly improve the ultrasound-based prediction of postnatal kidney survival in CAKUT.

Methods: Histological analysis of kidneys of 15 CAKUT foetuses was performed to better standardize the ultrasound interpretation of dysplasia and cysts. Ultrasound images of 140 CAKUT foetuses with 2-year postnatal follow-up were annotated for amniotic fluid volume and kidney number, size, dysplasia and/or cysts using a standardized ultrasound readout. Association of ultrasound features and clinical data (sex and age at diagnosis) with postnatal kidney function was studied using logistic regression. Amniotic fluid proteome related to kidney dysplasia or cysts was characterized by mass spectrometry.

Results: Histologically, poor ultrasound corticomedullary differentiation was associated with dysplastic lesions and ultrasound hyperechogenicity was associated with the presence of microcysts. Of all ultrasound and clinical parameters, reduced amniotic volume, dysplasia and cysts were the best predictors of poor outcome (odds ratio 57 [95% confidence interval (CI) 11-481], 20 [3-225] and 7 [1-100], respectively). Their combination into an algorithm improved prediction of postnatal kidney function compared with amniotic volume alone (area under the receiver operating characteristics curve 0.92 [95% CI 0.86-0.98] in a 10-fold cross-validation). Dysplasia and cysts were correlated (Cramer's V coefficient = 0.44, P < .0001), but amniotic fluid proteome analysis revealed that they had a distinct molecular origin (extracellular matrix and cell contacts versus cellular death, respectively), probably explaining the additivity of their predictive performances.

Conclusion: Antenatal clinical advice for CAKUT pregnancies can be improved by a more standardized and combined interpretation of ultrasound data.