Atypical anti-glomerular basement membrane disease with membranous hyperplasia: diagnostic challenges and treatment variability.

This case report presents a detailed analysis of a 31-year-old male patient who presented with a complex array of clinical symptoms, including proteinuria, hematuria, edema, and kidney insufficiency. Despite undergoing multiple tests, the results for anti-glomerular basement membrane antibodies yielded negative findings. Subsequently, kidney biopsy pathology revealed a distinct diagnosis of atypical anti-glomerular basement membrane (anti-GBM) disease with membrane hyperplasia. Treatment was initiated with a comprehensive approach involving high doses of corticosteroids therapy and cyclophosphamide (CTX). However, contrary to expectations, the patient's kidney function exhibited rapid deterioration following this therapeutic regimen. The culmination of these complications necessitated a pivotal transition to maintenance hemodialysis. This case underscores the intricate challenges associated with diagnosing and managing rare and atypical presentations of kidney disorders. The negative anti-GBM antibody results and subsequent identification of atypical anti-GBM nephropathy highlight the need for tailored diagnostic strategies to discern subtle nuances within complex clinical scenarios. Additionally, the unexpected response to the treatment regimen emphasizes the potential variability in individual patient responses, underlining the necessity for vigilant monitoring and adaptable treatment strategies. This case report contributes to the evolving understanding of atypical kidney pathologies and the complexities involved in their management.

Admission proteinuria predicts the incidence of acute kidney injury among patients with acute ST-segment elevation myocardial infarction: a retrospective cohort study.

BACKGROUND: Proteinuria indicates renal dysfunction and is associated with the development of acute kidney injury (AKI) in several conditions, but the association between proteinuria and AKI in patients with ST-segment elevation myocardial infarction (STEMI) remains unclear. This research aims to investigate the predictive value of proteinuria for the development of AKI in STEMI patients. METHODS: A total of 2735 STEMI patients were enrolled. The present study's endpoint was AKI incidence during hospitalization. AKI is defined according to the Kidney Disease: Improving Global Outcomes criteria. We defined proteinuria, measured with a dipstick, as mild (1+) or heavy (2+ to 4+). Multivariate logistic regression and subgroup analyses were used to testify to the association between proteinuria and AKI. RESULTS: Overall, proteinuria was observed in 634 (23.2%) patients. Multivariate logistic regression analyses revealed that proteinuria [odds ratio (OR), 1.58; 95% confidence interval (CI), 1.25-2.00; P  < 0.001] was the independent predictive factor for AKI. Severe proteinuria was associated with a higher adjusted risk for AKI compared with the nonproteinuria group (mild proteinuria: OR, 1.35; 95% CI, 1.04-1.75; P  = 0.025; severe proteinuria: OR, 2.50; 95% CI, 1.70-3.68; P  < 0.001). The association was highly consistent across all studied subgroups. (all P for interaction >0.05). CONCLUSION: Admission proteinuria measured using a urine dipstick is an independent risk factor for the development of AKI in STEMI patients.

Role of perirenal adiposity in renal dysfunction among CKD individuals with or without diabetes: a Japanese cross-sectional study.

INTRODUCTION: It remains unclear whether increased perirenal fat (PRF) accumulation is equally related to renal involvement in patients with and without diabetes mellitus (DM). We evaluated the association between PRF volume (PRFV) and low glomerular filtration rate (GFR) and proteinuria in people with or without type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We performed a cross-sectional analysis of 473 individuals without T2DM (non-DM, n=202) and with T2DM (DM, n=271). PRFV (cm3), obtained from non-contrast CT, was indexed as PRF index (PRFV/body surface area, cm3/m2). Multivariate-adjusted models were used to determine the ORs of PRFV and PRFV index for detecting estimated GFR (eGFR) decrease of <60 mL/min/1.73 m2 proteinuria onset, or both. RESULTS: Although body mass index (BMI), visceral fat area, and waist circumference were comparable between the non-DM and DM groups, kidney volume, PRFV, and PRFV index were higher in individuals with T2DM than in those without T2DM. In the multivariate analysis, after adjusting for age, sex, BMI, hypertension, smoking history, and visceral fat area ≥100 cm2, the cut-off values of PRFV index were associated with an eGFR<60 in individuals with DM (OR 6.01, 95% CI 2.20 to 16.4, p<0.001) but not in those without DM. CONCLUSIONS: PRFV is associated with low eGFR in patients with T2DM but not in those without T2DM. This suggests that PRF accumulation is more closely related to the onset and progression of diabetic kidney disease (DKD) than non-DKD. Clarifying the mechanisms through which PRF influences DKD development could pave the way for novel prevention and treatment strategies.

Mathematical expansion and clinical application of chronic kidney disease stage as vector field.

There are cases in which CKD progression is difficult to evaluate, because the changes in estimated glomerular filtration rate (eGFR) and proteinuria sometimes show opposite directions as CKD progresses. Indices and models that enable the easy and accurate risk prediction of end-stage-kidney disease (ESKD) are indispensable to CKD therapy. In this study, we investigated whether a CKD stage coordinate transformed into a vector field (CKD potential model) accurately predicts ESKD risk. Meta-analysis of large-scale cohort studies of CKD patients in PubMed was conducted to develop the model. The distance from CKD stage G2 A1 to a patient's data on eGFR and proteinuria was defined as r. We developed the CKD potential model on the basis of the data from the meta-analysis of three previous cohort studies: ESKD risk = exp(r). Then, the model was validated using data from a cohort study of CKD patients in Japan followed up for three years (n = 1,564). Moreover, the directional derivative of the model was developed as an index of CKD progression velocity. For ESKD prediction in three years, areas under the receiver operating characteristic curves (AUCs) were adjusted for baseline characteristics. Cox proportional hazards models with spline terms showed the exponential association between r and ESKD risk (p<0.0001). The CKD potential model more accurately predicted ESKD with an adjusted AUC of 0.81 (95% CI 0.76, 0.87) than eGFR (p<0.0001). Moreover, the directional derivative of the model showed a larger adjusted AUC for the prediction of ESKD than the percent eGFR change and eGFR slope (p<0.0001). Then, a chart of the transformed CKD stage was developed for implementation in clinical settings. This study indicated that the transformed CKD stage as a vector field enables the easy and accurate estimation of ESKD risk and CKD progression and suggested that vector analysis is a useful tool for clinical studies of CKD and its related diseases.

Acute kidney injury in hospitalized children with proteinuria: A multicenter retrospective analysis.

BACKGROUND AND OBJECTIVE: Acute kidney injury (AKI) is a common complication in hospitalized pediatric patients. Previous studies focused on adults found that proteinuria detected during an admission urinalysis is fit to serve as an indicator for AKI and associated clinical outcomes. The objective of this study is to evaluate if proteinuria on the first day of hospital services in hospitalized children is associated with AKI, need for renal replacement therapy, shock and/or antibiotic use, critical care services, and all-cause mortality at 30 days, hypothesizing that it is associated with these outcomes. METHODS: This is a retrospective cohort study using TriNetX electronic health record data of patients 2 to 18 years of age who underwent urinalysis laboratory testing on hospital admission, had three subsequent days of hospital or critical care services billing codes and creatinine laboratory values, and no pre-existing renal-related complex chronic condition. This study evaluated for the frequency, odds, and severity of AKI as defined by Kidney Disease: Improving Global Outcomes modified criteria and assessed for associated clinical outcomes. RESULTS: This study included 971 pediatric subjects [435 (44.7%) with proteinuria]. Proteinuria on the first day of hospital services was associated with an increased odds for higher severity AKI on any day of hospitalization (odds ratio [OR] 2.41, CI 1.8-3.23, p<0.001), need for renal replacement therapy (OR 4.58, CI 1.69-12.4, p = 0.001), shock and/or antibiotic use (OR 1.34, CI 1.03-1.75, p = 0.033), and all-cause mortality at 30 days post-admission (OR 10.0, CI 1.25-80.5, p = 0.013). CONCLUSION: Children with proteinuria on the first day of hospital care services may have an increased odds of higher severity AKI, need for renal replacement therapy, shock and/or antibiotic use, and all-cause mortality at 30 days post-admission, with no significant association found for critical care services, mechanical intubation, or inotrope or vasopressor use.

Efficacy and Safety of Hydroxychloroquine in Patients with IgA Nephropathy: A Meta-Analysis.

AIM: The purpose of this study was to determine efficacy and safety of hydroxychloroquine (HCQ) for patients with IgA nephropathy (IgAN). METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, Wanfang database, Chinese National Knowledge Infrastructure and VIP database up to February 2023 were searched for associated studies comparing HCQ with any other nonHCQ for treating IgAN. The effects of proteinuria, a 50% decrease in proteinuria, estimated glomerular filtration rate (eGFR) and adverse events in patients with IgAN were examined in a meta-analysis. Data were extracted and pooled using RevMan 5.3. RESULTS: Three randomized controlled trials (RCTs), two retrospective and two prospective studies (675 patients) that matched our inclusion criteria were identified. Compared with a control group, HCQ significantly reduced proteinuria (mean difference (MD): -0.26, 95% confidence interval (CI): -0.44 to -0.08, p < 0.01). Patients receiving HCQ plus renin-angiotensin system inhibitors (RASSi) had a better efficacy in proteinuria alleviation and a 50% decrease in proteinuria compared with control groups (MD: -0.38, 95% CI: -0.50 to -0.25, p < 0.001 and relative risk (RR) = 3.31, 95% CI: 1.73 to 6.36, p < 0.001). No appreciable variations were observed in eGFR between HCQ groups and control groups in treating patients with IgAN (MD: -2.00, 95% CI: -4.36 to 0.36, p = 0.10). Moreover, no serious adverse events were observed during HCQ treatment. CONCLUSIONS: Our results indicate HCQ is an efficient, secure treatment for IgAN.

Prognostic role of mesangial IgM deposition in IgA nephropathy: a long-term cohort study.

BACKGROUND: The clinical significance of mesangial immunoglobulin (Ig) M deposition in IgA nephropathy (IgAN) has been less explored and remains a topic of debate. Therefore, our study aimed to investigate the prognostic value of mesangial IgM deposition in a long-term follow-up cohort of IgAN patients. METHODS: A unicentric retrospective study was conducted on 93 consecutive IgAN patients (median age 41 years, 68% male, eGFR 48.7 mL/min, proteinuria 1.1 g/g) from 2010 to 2015. They were followed until end-stage kidney disease (ESKD), death, or until the end of the study in January 2021, with a median follow-up of 7 years. An independent pathologist evaluated the IgM immunofluorescence pattern, Oxford MEST-C score, and transmission electron microscopy (TEM) lesions following a comprehensive protocol. RESULTS: In our cohort, 70% had mesangial IgM-positive deposits, while 30% were IgM-negative. Both groups were similar in age, sex, prevalence of arterial hypertension, Charlson comorbidity scores, kidney function (eGFR and proteinuria), pathology findings (Oxford MEST-C score, IgG and C3 immune deposition), and TEM analysis. Treatment with RASI and immunosuppression, and death rates were also comparable. However, 37% of IgM-positive patients progressed to ESKD, significantly higher than the 11% in the IgM-negative group. Univariate and multivariate Cox proportional hazards regression analyses identified lower eGFR, higher Oxford MEST-C score, and mesangial IgM deposits as independent factors associated with shorter kidney survival. CONCLUSIONS: Our study highlights mesangial IgM deposition as a potential risk factor for ESKD in patients with advanced IgAN, laying a foundation for further research in this area.

Diagnostic value of renal biopsy in anti-phospholipase A2 receptor antibody-positive patients with proteinuria in China.

Renal biopsy remains the gold standard for diagnosing membranous nephropathy (MN). Recent studies have suggested that renal biopsy can be replaced with the serum phospholipase A2 receptor (PLA2R) antibody test for MN diagnosis in patients with nephrotic syndrome. However, this test has not been validated in the Chinese population. In this study, we investigated whether renal biopsy provides additional diagnostic information on patients with proteinuria who are seropositive for PLA2R antibodies (SAb +). We retrospectively reviewed the clinicopathological characteristics of SAb + adult patients (aged ≥ 18 years) with proteinuria (≥ 0.5 g/24 h) assessed at the Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, from June 2021 to March 2022. Among a total of 801 SAb + patients who received renal biopsy, those with incomplete pathological data, diabetes or any potential cause of secondary MN were excluded. Among the 491 remaining patients, 474 had primary MN (PMN), 16 had atypical MN (AMN, 9 patients with "full house" and 2 patients with HBsAg + /HBcAg + immunofluorescence results), and 1 had focal segmental glomerulosclerosis. In patients with an eGFR of ≥ 60 mL/min/1.73 m2 (n = 451), 436 had PMN, and 71 (16.3%) exhibited additional biopsy findings, with obesity-related glomerulopathy being the most common. In patients with an impaired eGFR (n = 40), 38 had PMN, and 31 (81.6%) showed additional findings, with acute tubular injury being the most common. In conclusion, anti-PLA2R antibody positivity is highly predictive of PMN in Chinese adults but often coexists with other pathological diagnoses. The advantages of renal biopsy for detecting other pathologies should be weighed against the potential risks of the biopsy procedure.

Clinicopathologic Study of Sickle Cell-associated Kidney Disease: A Nigerian Experience.

BACKGROUND: Improvements in sickle cell disease (SCD) care have resulted in the survival of many patients into adulthood, although this is accompanied by the increased incidence of end-organ damage, including chronic kidney disease (CKD). OBJECTIVES: This study assessed the prevalence, pattern and predictors of renal dysfunction in SCD patients and investigated the associated renal histopathologic changes. METHODS: We evaluated 105 patients with SCD, for proteinuria, estimated glomerular filtration rate (eGFR), and tubular dysfunction. Renal biopsy was conducted on 22 patients who qualified. Data were analysed using SPSS package version 23. RESULTS: Thirty-seven (35.2%) of the 105 patients had CKD, as defined by an eGFR of 60 ml/min/1.73 m2 and/or proteinuria. The fractional excretion of potassium (FEK) was elevated in all patients, whereas the fractional excretion of sodium (FENa) was elevated in 98.1%. Glomerular filtration rate was negatively correlated with irreversible percentage sickle cell count (r = -0.616, P = 0.0001), FEK (r = -0.448, P = 0.0001) and FENa (r = -0.336, P = 0.004). Age, irreversible percentage sickle cell count, haemoglobin levels and FENa were the major predictors of CKD. The histological pattern in the 22 patients who had biopsies was consistent with mesangioproliferative glomerulonephritis 11 (50%), minimal change disease 6 (27.3%), focal segmental glomerulosclerosis 3 (13.6%) and interstitial nephritis 2 (9.1%). CONCLUSIONS: CKD was prevalent in SCD patients, and it was characterised by tubular dysfunction and mesangioproliferative glomerulonephritis. The main predictors of CKD were increased age, severity of vaso-occlusive crisis, worsening anaemia and tubular dysfunction.

Treatment of Nutcracker Syndrome with Left Renal Vein Transposition and Endovascular Stenting.

BACKGROUND: Nutcracker syndrome is a rare condition that occurs as a result of the entrapment of the left renal vein (LRV) between the aorta and the superior mesenteric artery. It is typically associated with symptoms such as left flank pain, hematuria, proteinuria, and pelvic congestion. The current treatment approach may be conservative in the presence of tolerable symptoms, and surgical or hybrid and stenting procedures in the order of priority in the presence of intolerable symptoms. The aim of this study is to review our experiences to evaluate the results of both methods in this series in which we have a greater tendency toward surgery instead of stenting. METHODS: The clinical data of consecutive patients with nutcracker syndrome who underwent LRV transposition and LRV stenting between July 2019 and October 2023 were retrospectively reviewed. The patients were divided into 2 groups based on the methods of treatment: surgical and stenting. For procedure selection, LRV transposition was primarily recommended, with stenting offered to those who declined. Primary end points were morbidity and mortality. Secondary end points included late complications, patency, freedom from reintervention, and resolution of symptoms. Standard basic statistics and survival analysis methods were employed. RESULTS: Nineteen patients with nutcracker syndrome (female: 100%) were treated with LRV stentings (n = 5) and LRV transposition (n = 14). The mean age was 24 (20-27, interquartile range [IQR]) years. The mean follow-up was 23 (9-32, IQR) months. There were no major complications and mortality after both procedures. The most frequent sign and symptom associated with LRV entrapment were left flank pain 100% (n = 19), proteinuria 88% (n = 15), and hematuria 47% (n = 9). The mean peak velocity ratio on Doppler ultrasound was 6.13 (6-6.44, IQR). Aortomesenteric angle, beak angle (beak sign), and mean diameter ratio on computed tomography were 26° (22.6-28.5, IQR), 25° (23.9-28, IQR), and 5.3 (5-6, IQR), respectively. Venous pressure measurements were only used to confirm the diagnosis in 5 patients in the stenting group. The measured renocaval gradient was 4 (3.9-4.4, IQR) mm Hg. After both procedures, the classical symptoms, including left flank pain, proteinuria, and hematuria, resolved in 89.5% (n = 17), 57.8% (n = 11), and 82.3% (n = 15) of the cases, respectively. A total of 4 patients required reintervention, 3 patients after LRV transposition (occlusion, n = 2; stenosis, n = 1), and 1 patient after stenting (occlusion, n = 1). The 1-year and 3-year primary patency for the 19 patients was 87% and 80%, respectively. Three-year primary-assisted patency was 100%. Similarly, the 1-year and 3-year freedom from reintervention rate was 83% and 72%, respectively. Additionally, the 1-year and 3-year primary patency for the surgical group was 91% and 81%, respectively, and the 1-year and 3-year primary patency for the stenting group was 75%. CONCLUSIONS: Nutcracker syndrome should be kept in mind in cases where flank pain and hematuria cannot be associated with kidney diseases. Radiographic evidence must be accompanied by serious symptoms to initiate the treatment of nutcracker syndrome with LRV transposition and endovascular stenting procedures. Both procedures, along with their respective advantages and disadvantages, can be preferred as primary treatments for nutcracker syndrome. Our study demonstrates that both procedures can be safely and effectively performed, yielding good outcomes.

Neonatal nephrotic syndrome: all is not gloomy.

Congenital nephrotic syndrome (CNS) is a rare clinical syndrome with a constellation of proteinuria, hypoalbuminaemia and oedema, presenting within 3 months of birth. We present a rare case of neonatal nephrotic syndrome with a probable sepsis induced aetiology. The neonate was referred at day of life 15 with Klebsiella pneumonia sepsis and anasarca. On investigation, the patient had nephrotic range proteinuria, hypoalbuminaemia, generalised anasarca and ascites. The neonate was started on broad-spectrum antibiotics and furosemide. Genetic and other secondary causes of CNS were ruled out. With supportive management and resolution of sepsis, the neonate improved. This case highlights the rare cause of sepsis-induced nephrotic syndrome (NS), which required only supportive treatment without the need for aggressive management of CNS.

Early-Stage Chronic Kidney Disease and Related Health Care Spending.

Importance: The global burden of chronic kidney disease (CKD) is substantial and potentially leads to higher health care resource use. Objective: To examine the association between early-stage CKD and health care spending and its changes over time in the general population. Design, Setting, and Participants: Cohort study using nationwide health checkup and medical claims data in Japan. Participants included individuals aged 30 to 70 years with estimated glomerular filtration rates (eGFR) of 30 mL/min/1.73 m2 or greater at the baseline screening in 2014. Data analyses were conducted from April 2021 to October 2023. Exposure: The CKD stages at baseline, defined by the eGFR and proteinuria, were as follows: eGFR of 60 mL/min/1.73 m2 or greater without proteinuria, eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. Main Outcome and Measures: The primary outcome was excess health care spending, defined as the absolute difference in health care spending according to the baseline CKD stages (reference group: eGFR ≥60 mL/min/1.73 m2 without proteinuria) in the baseline year (2014) and in the following 5 years (2015 to 2019). Results: Of the 79 988 participants who underwent a health checkup (mean [SD] age, 47.0 [9.4] years; 22 027 [27.5%] female), 2899 (3.6%) had an eGFR of 60 mL/min/1.73 m2 or greater with proteinuria, 1116 (1.4%) had an eGFR of 30 to 59 mL/min/1.73 m2 without proteinuria, and 253 (0.3%) had an eGFR of 30 to 59 mL/min/1.73 m2 with proteinuria. At baseline, the presence of proteinuria and an eGFR less than 60 mL/min/1.73 m2 were associated with greater excess health care spending (adjusted difference, $178; 99% CI, $6-$350 for proteinuria; $608; 99% CI, $233-$983 for an eGFR of 30-59 mL/min/1.73 m2; and $1254; 99% CI, $134-$2373 for their combination). The study consistently found excess health care spending over the following 5 examined years. Conclusions and Relevance: In this cohort study of nationwide health checkup and medical claims data in Japan, early-stage CKD was associated with excess health care spending over the 5 examined years, and the association was more pronounced with a more advanced disease stage.

Combination of allopurinol with Dahuang Mudan Tang significantly improve kidney function and alleviate oxidative stress and inflammation of chronic kidney disease stage â -â ¢ patients with hyperuricemia.

OBJECTIVE: To evaluate the effect of Dahuang Mudan Tang (, DHMD) and allopurinol on the treatment of chronic kidney disease staged G1-G3b patients with hyperuricemia and to provide novel insights into the clinical management of chronic kidney disease complications. METHODS: A total of 80 chronic kidney patients staged G1-G3b with hyperuricemia were randomly grouped to receive single allopurinol treatment (control) and combined treatment with DHMD (treated) for 8 weeks. The kidney function and proteinuria indicators of patients were compared between pre-and post-treatment. The oxidative stress and inflammation responses were evaluated by corresponding indicators and cytokines. The clinical efficiency rate and adverse reaction events were also summarized to assess the therapeutic efficiency and safety. RESULTS: The kidney function and proteinuria of enrolled patients were alleviated after their therapies, behaved as the increasing estimated glomerular filtration rate and decreasing serum creatinine, serum uric acid, urea nitrogen, 24 h urine protein levels. On the other hand, the malondialdehyde level and pro-inflammation cytokines were suppressed by the therapies, and the superoxide dismutase was found to be significantly enhanced. Patients in the treated groups showed a better recovery in kidney function, proteinuria, oxidative stress, and inflammation response. Moreover, patients in the treated group showed a higher efficiency rate (95%) and fewer adverse reaction events (5%). CONCLUSIONS: The combination of allopurinol with DHMD significantly promoted the recovery of chronic kidney disease stage G1-G3b patients with hyperuricemia, which can be considered a novel clinical therapeutic strategy.

Role of novel biomarker monocyte chemo-attractant protein-1 in early diagnosis & predicting progression of diabetic kidney disease: A comprehensive review.

Diabetic kidney disease (DKD) is the most devastating complication of diabetes mellitus. Identification of patients at the early stages of progression may reduce the disease burden. The limitation of conventional markers such as serum creatinine and proteinuria intensify the need for novel biomarkers. The traditional paradigm of DKD pathogenesis has expanded to the activation of the immune system and inflammatory pathways. Monocyte chemo-attractant protein-1 (MCP-1) is extensively studied, as a key inflammatory mediator that modulates the development of DKD. Recent evidence supports the diagnostic role of MCP-1 in patients with or without proteinuria in DKD, as well as a significant role in the early prediction and risk stratification of DKD. In this review, we will summarize and update present evidence for MCP-1 for diagnostic ability and predicting the progression of DKD.

The relation between proteinuria and the severity of COVID-19.

BACKGROUND: The association between proteinuria, which is also an indicator of chronic kidney disease (CKD), and coronavirus disease 2019 (COVID-19) severity is unclear. METHODS: We selected 342 hospitalized patients with COVID-19 diagnosed via polymerase chain reaction testing between February 2020 and October 2022 and who had at least one urinalysis 14-365 days before admission. RESULTS: Proteinuria before admission was associated neither with oxygen administration nor developing pneumonia in multivariate analysis (odds ratio [OR] 1.03; 95% confidence interval (CI) 0.44-2.40, p = 0.95 and OR 1.01; 95% CI 0.47-2.17, p = 0.98, respectively). Proteinuria on admission was associated both with oxygen administration and developing pneumonia in multivariate analysis (OR 3.29; 95% CI 1.37-7.88, p < 0.01 and OR 3.81; 95% CI 1.68-8.62, p < 0.01, respectively). The percentage of patients with proteinuria on admission was significantly higher than those before admission (37.4% vs. 17.8%; p < 0.01). In the subgroup analysis, proteinuria on admission among patients with eGFR ≥ 60 mL/min/1.73 m2 was associated with both oxygen administration and developing pneumonia (OR 4.86; 95% CI 1.22-19.38, p = 0.03, OR 3.65; 95% CI 1.06-12.58, p = 0.04, respectively). In contrast, proteinuria on admission among patients with eGFR < 60 mL/min/1.73 m2 was associated with developing pneumonia (OR 6.45; 95%CI 1.78-23.35, p = 0.01), not with oxygen administration (OR 3.28; 95% CI 0.92-11.72, p = 0.07). CONCLUSIONS: Although underlying proteinuria before admission was not associated with COVID-19 severity, proteinuria on admission was associated with oxygen demand and developing pneumonia.

Renal Function Impairment in Children With Congenital Cytomegalovirus Infection: A Cross-sectional Study.

BACKGROUND: We aimed to determine the prevalence and severity of glomerular and tubular renal dysfunction by means of urinalysis in infants and toddlers with congenital cytomegalovirus infection (cCMV) and their association with cCMV disease, viruria and antiviral treatment. METHODS: This cross-sectional study was done using the Spanish Registry of Congenital Cytomegalovirus Infection. First-morning urine samples were collected from January 2016 to December 2018 from patients <5 years old enrolled in Spanish Registry of Congenital Cytomegalovirus Infection. Samples were excluded in case of fever or other signs or symptoms consistent with acute infection, bacteriuria or bacterial growth in urine culture. Urinary protein/creatinine and albumin/creatinine ratios, urinary beta-2-microglobulin levels, hematuria and CMV viruria were determined. A 0.4 cutoff in the urinary albumin/protein ratio was used to define tubular (<0.4) or glomerular (>0.4) proteinuria. Signs and symptoms of cCMV at birth, the use of antivirals and cCMV-associated sequelae at last available follow-up were obtained from Spanish Registry of Congenital Cytomegalovirus Infection. RESULTS: Seventy-seven patients (37 females, 48.1%; median [interquartile range] age: 14.0 [4.4-36.2] months) were included. Symptom-free elevated urinary protein/creatinine and albumin/creatinine ratios were observed in 37.5% and 41.9% of patients, respectively, with tubular proteinuria prevailing (88.3%) over glomerular proteinuria (11.6%). Proteinuria in the nephrotic range was not observed in any patients. In multivariate analysis, female gender was the only risk factor for tubular proteinuria (adjusted odds ratio = 3.339, 95% confidence interval: 1.086-10.268; P = 0.035). cCMV disease at birth, long-term sequelae, viruria or the use of antivirals were not associated with urinalysis findings. CONCLUSIONS: Mild nonsymptomatic tubular proteinuria affects approximately 40% of infants and toddlers with mostly symptomatic cCMV in the first 5 years of life.

Study of prevalence, clinical profile, and predictors of rapid progression in diabetic kidney disease.

BACKGROUND: A significant proportion of diabetic kidney disease (DKD) experience a rapid decline in eGFR, leading to end-stage kidney disease (ESKD) within months. This single-centered retrospective cohort study aimed to assess the prevalence, clinical profile, and predictors for rapid progression in type 2 diabetes mellitus (T2DM) patients with DKD. METHOD: Three hundred fifty-nine T2DM patients with DKD between January 2018 and 2022 were included and those with superimposed non-diabetic kidney disease, chronic kidney disease 5, and < 6 months follow-up were excluded. They were classified as rapid and non-rapid progressors based on the annual eGFR decline of > 5 ml/min/1.73 m2/year. The primary outcome analyzed was the progression to ESKD. The secondary outcomes were the onset of microvascular and macrovascular complications and predictors for rapid progression as well as ESKD. RESULTS: In a median follow-up of 3.5 years, 61.3% were rapid progressors (mean eGFR decline of 15.4 ml/1.73m2/year) and 38.7% were non-rapid progressors (mean eGFR decline 1.8 ml/1.73m2/year. Among rapid progressors, 61.4% reached ESKD. Severe proteinuria, the presence of retinopathy, and acute kidney injury (AKI) episodes were strong predictors of rapid progression. Cardiovascular disease and diabetic retinopathy (microvascular complications) were significantly higher among rapid progressors and had a mortality rate of 7.2%. CONCLUSION: The majority of type 2 DKD patients were rapid progressors and two-thirds of them developed ESKD. The prevalence of hypertension, cardiovascular disease, diabetic retinopathy, AKI episodes, and mortality was higher in rapid progressors. Severe proteinuria and diabetic retinopathy were found to be strong predictors for rapid eGFR decline and its progression to ESKD.

Therapeutic Exercise on Metabolic and Renal Outcomes in Patients with Chronic Kidney Disease: A Narrative Review.

BACKGROUND: Chronic kidney disease (CKD) affects 11-13% of the world population. The main risk factors for CKD include diabetes, hypertension, and obesity. Metabolic syndrome (MS) is associated with the onset of CKD in the nondiabetic population. Obesity and MS are also risk factors for a worse progression of established CKD. Therapeutic exercise is an effective option to treat and manage obesity, MS, and diabetes in the general population. However, the evidence on the effect of exercise on patients with CKD, obesity, and MS is scarce. SUMMARY: We evaluated available evidence on the effect of therapeutic exercise in patients with CKD, excluding dialysis, particularly in improving the metabolic risk factors and main renal outcomes: renal function loss and albuminuria/proteinuria. This review includes prospective studies and clinical trials. A total of 44 studies were analysed in 1,700 subjects with renal disease (2-5), including patients with renal transplantation. Most studies did not prove a major effect of exercise on albuminuria/proteinuria, glomerular filtration rate (GFR), obesity, or MS. These results are intriguing and deserve attention. The exploratory nature of most studies, including a low number of cases and short follow-up, might explain the lack of efficacy of exercise in our analysis. Specific aspects like the type of exercise, frequency, intensity, duration, accommodation during follow-up, individualization, safety, and adherence are crucial to the success of therapeutic exercise. The beneficial role of exercise in patients with CKD remains to be determined. KEY MESSAGES: Key messages of this review are as follows. (1) The effect of therapeutic exercise on renal and metabolic outcomes in patients with CKD remains to be determined. (2) According to the evidence selected, therapeutic exercise seems to be safe to treat patients with CKD. (3) Most studies are exploratory by nature, with results that need further investigation. (4) Therapeutic exercise is a complex procedure that must be specifically designed to treat patients with CKD.

Does obesity really affect renal transplantation outcomes?

INTRODUCTION: Kidney transplantation is the treatment of choice for patients with stage 5 chronic kidney disease (CKD). About 60% of CKD patients are overweight or obese at the time of kidney transplantation, and post-transplant obesity occurs in 50% of patients, with a weight gain of 10% in the first year and high risk of cardiovascular mortality. Obesity is associated with an increased risk of delayed graft function (DGF), acute rejection, surgical complications, graft loss and mortality. The aim of this study is to assess the clinical evolution of obese and overweight patients that have received a kidney transplant, based on short- and long-term complications associated with a higher BMI. MATERIAL AND METHODS: A descriptive, observational, cross-sectional study was conducted with 104 kidney or pancreas-kidney transplant patients between March 2017 and December 2020, with a follow-up until April 2021. For comparative analysis, patients were grouped according to BMI. RESULTS: Mean age was of 56.65 years, 60.6% male and 39.4 % female. Overweight patients experienced prolonged surgeries, more surgical wound dehiscence, delayed graft function, hernias, proteinuria and more indications for renal biopsies. Additionally, obese patients displayed more DGF, indications for renal biopsies, proteinuria, development of diabetes mellitus, atrial fibrillation and needed prolonged hospital stays. CONCLUSIONS: Despite a high prevalence of comorbidity in the overweight and/or obese population, we found no reduction in patient and/or graft survival. However, longer follow-up is needed.

Tubular toxicity of proteinuria and the progression of chronic kidney disease.

Proteinuria is a well-established biomarker of chronic kidney disease (CKD) and a risk predictor of associated disease outcomes. Proteinuria is also a driver of CKD progression toward end-stage kidney disease. Toxic effects of filtered proteins on proximal tubular epithelial cells enhance tubular atrophy and interstitial fibrosis. The extent of protein toxicity and the underlying molecular mechanisms responsible for tubular injury during proteinuria remain unclear. Nevertheless, albumin elicits its toxic effects when degraded and reabsorbed by proximal tubular epithelial cells. Overall, healthy kidneys excrete over 1000 individual proteins, which may be potentially harmful to proximal tubular epithelial cells when filtered and/or reabsorbed in excess. Proteinuria can cause kidney damage, inflammation and fibrosis by increasing reactive oxygen species, autophagy dysfunction, lysosomal membrane permeabilization, endoplasmic reticulum stress and complement activation. Here we summarize toxic proteins reported in proteinuria and the current understanding of molecular mechanisms of toxicity of proteins on proximal tubular epithelial cells leading to CKD progression.