Nephron最新文献

Background: In daily practice, glomerular filtration rate (GFR) is estimated with equations including renal biomarkers. Among these biomarkers, serum creatinine remains the most used. However, there are many limitations with serum creatinine, which we will discuss in the current review. We will also discuss how creatinine-based equations have been developed and what we can expect from them in terms of performance to estimate GFR.

Summary: Different creatinine-based equations have been proposed. We will show the advantages of the recent European Kidney Function Consortium equation. This equation can be used in children and adults. This equation can also be used with some flexibility in different populations.

Key messages: GFR is estimated by creatinine-based equations, but the most important for nephrologists is probably to know the limitations of these equations.

Hereditary xanthinuria (HXAN) is a rare metabolic disorder that results from mutations in either the xanthine dehydrogenase (XDH) or the molybdenum cofactor sulfurase genes (MOCOS), respectively defining HXAN type I and type II. Hypouricemia, hypouricosuria, and abnormally high plasma and urine levels of xanthine, causing susceptibility to xanthine nephrolithiasis and deposition of xanthine crystals in tissues, are the metabolic hallmarks of HXAN. Several pathogenic variants in the XDH gene have so far been identified in patients with HXAN type I, but the clinical phenotype associated with the whole deletion of the human XDH gene is unknown. Herein, we report the case of a woman diagnosed with HXAN, whose molecular genetic testing revealed a homozygous microdeletion involving the XDH gene. Distinctive features of her medical history were the diagnosis of arterial hypertension and microalbuminuria at 22 years of age; a single pregnancy at the age of 25, complicated by proteinuria and transient kidney function deterioration in the third trimester; unexplained severe hypouricemia incidentally discovered during pregnancy; inability to breastfeed her newborn daughter due to primary agalactia; chronic kidney disease (CKD) stage 3 diagnosed at age 35; and progression to end-stage kidney disease over the next 12 years. Protocol noninvasive laboratory and imaging investigation was not informative as to the cause of CKD. This is the first description of the clinical phenotype associated with a natural knockout of the human XDH gene. Despite the lack of kidney histopathology data, the striking similarities with the phenotypes exhibited by comparable murine models validate the latter as useful sources of mechanistic insights for the pathogenesis of the human disease, supporting the hypothesis that the absence of xanthine dehydrogenase activity might represent a susceptibility factor for chronic tubulointerstitial nephritis, even in patients without kidney stones.

Introduction: Suppressor of cytokine signaling 3 (SOCS3) is highly expressed in mice with renal ischemia/reperfusion (RI/R) injury and has the potential to regulate mitophagy. On this basis, this study further investigates the possible mechanism via which SOCS3 affects RI/R by regulating mitophagy.

Method: After establishing a RI/R injury mouse model and a hypoxia/reoxygenation (H/R) cell model, the effects of silenced SOCS3 on injury and mitophagy in the above models were analyzed by ELISA, quantitative real-time polymerase chain reaction, Western blot, pathological sections, CCK-8 assay, flow cytometry, and JC-1 assay. Mechanistic studies were carried out with the help of database analysis and binding validation experiments (chromatin immunoprecipitation, dual-luciferase reporter assay, and co-immunoprecipitation). After the binding target was identified, the regulatory relationship between the target gene and SOCS3 was verified by rescue experiments.

Result: The large increase in blood urea nitrogen (BUN) and creatinine (Cr) levels verified the success of the RI/R model. SOCS3 expression was up-regulated in RI/R mice. Silenced SOCS3 alleviated kidney damage and mitochondrial abnormalities in RI/R mice and inhibited mitophagy at the molecular level. Likewise, silenced SOCS3 alleviated H/R-induced cell damage and mitophagy. Finally, activating transcription factor 3 (ATF3) was determined to bind to the promoter of SOCS3, which interacted with insulin-like growth factor 1 receptor (IGF1R). Rescue experiments confirmed the effect of ATF3 on SOCS3 expression and the underlying regulatory mechanism.

Conclusion: ATF3 mediates SOCS3 expression to promote the activation of mitophagy, thereby aggravating renal ischemia-reperfusion injury.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited condition; however, its relationship with renal cell carcinoma (RCC) remains unclear. This paper aims to establish the prevalence of RCC and its subtypes amongst ADPKD patients.

Methods: A database search was conducted to retrieve studies reporting RCC occurrence within ADPKD patients until July 2023. Key outcomes included number and subtype of RCC cases, and number of RCCs presenting incidentally. A random-effects meta-analysis was performed.

Results: Our search yielded 569 articles, 16 met the inclusion criteria. Nephrectomy specimens from 1,147 ADPKD patients were identified. Of studies reporting per-kidney results (n = 13), 73 RCCs were detected amongst 1,493 kidneys, equating to a per-kidney prevalence of 4.3% (95% CI, 3.1-5.7, I2 = 15.7%). 75 ADPKD patients were found to have RCC (75/1,147), resulting in a per-person prevalence of 5.7% (95% CI, 3.7-7.9, I2 = 40.3%) (n = 16). As 7 patients had bilateral disease, 82 RCCs were detected in total. Of these, 39 were clear cell RCC, 35 were papillary and 8 were other. As such, papillary RCCs made up 41.1% (95% CI, 25.9-56.9, I2 = 18.1%) of detected cancers. The majority of RCCs were detected incidentally (72.5% [95% CI, 43.7-95.1, I2 = 66.9%]).

Conclusion: ADPKD appears to be associated with the papillary RCC subtype. The clinical implications of these findings are unclear, however, may become apparent as outcomes and life expectancy amongst APDKD patients improve.

Fabry Update.

Background: Thrombotic microangiopathy (TMA) is an important risk factor for the prognosis of lupus nephritis (LN). Patients with LN complicated with TMA tend to be critically ill with high mortality and poor prognosis. In the present study, we retrospectively analyzed the clinical manifestations, laboratory results, renal pathological manifestations, and prognosis of children with LN-TMA and analyzed the risk factors for end-stage renal disease (ESRD) in children with LN-TMA.

Methods: Seventy-four patients with LN and renal TMA (rTMA) were selected and compared to 128 LN controls without TMA (1:2 ratio) matched according to demographics, pathological type and treatments.

Results: The mean values of systolic blood pressure, diastolic blood pressure (DBP), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), urinary protein quantitation (PRO), urine red blood cells, N-acetyl-β-D-glucosidase (NAG), retinol-binding protein, systemic lupus erythematosus disease activity score (SLEDAI), and activity index (AI) scores in the TMA group were all higher than those in the non-TMA group (p < 0.05 and p < 0.01). The mean values of complement C3, hemoglobin, platelets, estimated glomerular filtration rate, and chronic index (CI) score in the TMA group were all lower than those in the non-TMA group (p < 0.05 and p < 0.01). The number of cases of glomerular crescent, fibrous crescent, endocapillary proliferation, tubular atrophy, interstitial fibrosis, C3 and C1q deposition in the TMA group was higher than that in the non-TMA group (p < 0.05 and p < 0.01). The 3-year and 5-year renal survival rates in the TMA group (88.93% vs. 97.00%, p < 0.05) and TMA group (61.41% vs. 82.31%, p < 0.05) were significantly lower than those in the non-TMA group. Multivariate Cox regression analysis showed that serum creatinine before treatment (≥110 μmol/L), TMA and interstitial fibrosis were independent risk factors for the development of ESRD in LN children.

Conclusion: The general condition of children with TMA is critical, and the prognosis is poor. Early detection, early treatment and the development of new treatments are key to improving LN-TMA outcomes in children.

Introduction: Multiple myeloma (MM) frequently involves the kidneys, resulting in acute, subacute, or chronic kidney disease (CKD). Patient- and treatment-related factors are associated with the long-term development of CKD. The aim of our study was to examine the association of serum free light chain (FLC) levels, measured at the time of diagnosis of MM, and CKD at subsequent follow-up.

Methods: Patients with newly diagnosed MM were identified using cancer registries at five hospitals. The primary outcome was low eGFR (<60 mL/min/1.73 m2) or dialysis dependence and a secondary composite outcome of low eGFR, dialysis dependence, or death at the last follow-up, up to 12 months from diagnosis. Logistic regression analyses were performed.

Results: A total of 149 patients met the inclusion criteria. Patients with an FLC level above the median had a higher frequency of hypertension (54% vs. 81%; p < 0.001), hyperlipidemia (37% vs. 56%; p = 0.018), low eGFR at the time of diagnosis (43% vs. 66%; p = 0.006), and a higher MM stage (p = 0.018). On multivariable analyses, after adjustment for several covariates, serum FLC level (per each 100 mg/L) was independently associated with low eGFR or dialysis dependence at follow-up (adjusted odds ratio [aOR] 1.021; 95% CI: 1.002, 1.041; p = 0.033). This association persisted for the composite outcome of low eGFR, dialysis dependence, or death (aOR 1.034; 95% CI: 1.006, 1.063; p = 0.018).

Discussion/conclusion: Higher serum FLC level measured at the time of MM diagnosis is independently associated with CKD at up to 12 months of follow-up.

The complement system, a cornerstone of the innate immune defense, typically confers protection against pathogens. However, in various clinical scenarios the complement's defensive actions can harm host cells, exacerbating immune and inflammatory responses. The central components C3 and C5 undergo proteolytic cleavage during complement activation, yielding small active fragments C3a and C5a anaphylatoxins. Traditionally, these fragments were associated with inflammation via the specific receptors C3a receptor (R), C5aR1 and C5aR2. Recent insights, however, spotlight the excessive C3a/C3aR and C5a/C5aR1 signaling as culprits in diverse disorders of inflammatory and autoimmune etiology. This is particularly true for several kidney diseases, where the potential involvement of anaphylatoxins in renal damage is supported by the enhanced renal expression of their receptors and the high levels of C3a and C5a in both plasma and urine. Furthermore, the production of complement proteins in the kidney, with different renal cells synthesizing C3 and C5, significantly contributes to local tissue injury. In the present review, we discuss the different aspects of C3a/C3aR and C5a/C5aR signaling in acute and chronic kidney diseases and explore the therapeutic potential of emerging targeted drugs for future clinical applications.

Aims: Hospital readmissions due to recurrent fluid overload in diabetes and diabetic kidney disease can be avoided with evidence-based interventions. We aimed to identify at-risk patients who can benefit from these interventions by developing risk prediction models for readmissions for fluid overload in people living with diabetes and diabetic kidney disease.

Methods: This was a single-center retrospective cohort study of 1,531 adults with diabetes and diabetic kidney disease hospitalized for fluid overload, congestive heart failure, pulmonary edema, and generalized edema between 2015 and 2017. The multivariable regression models for 30-day and 90-day readmission for fluid overload were compared with the LACE score for discrimination, calibration, sensitivity, specificity, and net reclassification index (NRI).

Results: Readmissions for fluid overload within 30 days and 90 days occurred in 8.6% and 17.2% of patients with diabetes, and 8.2% and 18.3% of patients with diabetic kidney disease, respectively. After adjusting for demographics, comorbidities, clinical parameters, and medications, a history of alcoholism (HR 3.85, 95% CI: 1.41-10.55) and prior hospitalization for fluid overload (HR 2.50, 95% CI: 1.26-4.96) were independently associated with 30-day readmission in patients with diabetic kidney disease, as well as in individuals with diabetes. Additionally, current smoking, absence of hypertension, and high-dose intravenous furosemide were also associated with 30-day readmission in individuals with diabetes. Prior hospitalization for fluid overload (HR 2.43, 95% CI: 1.50-3.94), cardiovascular disease (HR 1.44, 95% CI: 1.03-2.02), eGFR ≤45 mL/min/1.73 m2 (HR 1.39, 95% CI: 1.003-1.93) was independently associated with 90-day readmissions in individuals with diabetic kidney disease. Additionally, thiazide prescription at discharge reduced 90-day readmission in diabetic kidney disease, while the need for high-dose intravenous furosemide predicted 90-day readmission in diabetes. The clinical and clinico-psychological models for 90-day readmission in individuals with diabetes and diabetic kidney disease had better discrimination and calibration than the LACE score. The NRI for the clinico-psychosocial models to predict 30- and 90-day readmissions in diabetes was 22.4% and 28.9%, respectively. The NRI for the clinico-psychosocial models to predict 30- and 90-day readmissions in diabetic kidney disease was 5.6% and 38.9%, respectively.

Conclusion: The risk models can potentially be used to identify patients at risk of readmission for fluid overload for evidence-based interventions, such as patient education or transitional care programs to reduce preventable hospitalizations.

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) disease entity primarily attributed to genetic or acquired abnormalities in the alternative complement pathway. TMA can manifest in kidney transplant (KT) recipients owing to various factors, resulting in diverse clinical presentations. Given its adverse effects on allograft function and patient prognosis, genetic diagnostic approaches for aHUS are essential. Although rarely associated with diffuse alveolar hemorrhage, only a few mild cases have been reported to date. In this report, we present a case of the patient who experienced recurrent and life-threatening diffuse alveolar hemorrhage shortly after KT accompanied by graft failure.

Case presentation: An 18-year-old girl who underwent deceased donor KT developed recurrent diffuse alveolar hemorrhage with acute kidney injury, leading to graft failure. Microangiopathic hemolytic anemia, thrombocytopenia, and schistocytes in blood smears suggested the presence of TMA. The patient underwent therapeutic plasma exchange, and clinical condition improved during the procedure. Genetic testing confirmed a heterozygous c.1273C>T mutation in C3 gene, leading to the diagnosis of aHUS. However, after discontinuing the plasma exchange, the patient experienced seizures, recurrent pulmonary hemorrhage, and oliguria with recurring TMA features. The patient subsequently underwent eculizumab treatment, which resulted in complete remission, although hemodialysis was continued after graft nephrectomy.

Conclusion: In patients presenting with unexplained pulmonary hemorrhage and kidney injury following KT, genetic aHUS should be considered as a potential differential diagnosis for TMA.