Management of Peritoneal Dialysis-Associated Emergencies during the COVID-19 Pandemic: The Experience of a Center of Excellence.

The COVID-19 pandemic struck unexpectedly; emergency services and chronic care institutions, including dialysis centers, were overloaded. A significant problem was the care of COVID-positive patients alongside the care of chronically dialyzed patients who presented emergencies. In our hospital, which became a COVID support center for dialysis patients with severe forms of the disease, we had to care for PD patients with dialysis-related emergencies. We present two cases of patients managed on an outpatient basis or 1-day hospitalization who were treated successfully without compromising the quality of the care provided. We used remote monitoring, worked in a multidisciplinary team, and shortened the duration of the patients' hospitalization (and implicitly the risk of contact). In pandemic conditions, the advantage of PD was the possibility of patient isolation; in the first 6 months of the pandemic, we recorded no deaths in this category of patients. In hemodialysis patients, infection and mortality rates were high. Although we expected an increase in the number of peritoneal dialysis patients in the post-pandemic period, this did not happen. We continue to plead for the popularization of the PD method among patients and doctors, which has proven advantages in pandemic conditions.

Clinicopathological Characteristics and Disease Chronicity in Glomerular Diseases: A Decade-Long Study at Romania's Largest Kidney Biopsy Reference Center.

Glomerular diseases (GDs), significant causes of end-stage kidney disease, are better understood through epidemiological studies based on kidney biopsies (KBs), which provide important insights into their prevalence and characteristics. This study aims to analyze the clinicopathological features of GDs diagnosed from 2008 to 2017 at Romania's largest reference center. In this decade-long study, 1254 adult patients diagnosed with GDs were included. The local previously validated renal histopathological prognostic score was calculated for each KB using four histopathologic lesions: global glomerulosclerosis, tubular atrophy, interstitial fibrosis and fibrocellular/fibrous crescents. The mean patient age was 50 years, with a male predominance (57%). The primary referral reasons were nephrotic syndrome (46%), nephritic syndrome (37%), chronic kidney disease (12%), asymptomatic urinary abnormalities (4%), and acute kidney injury (1%). Immunoglobulin A nephropathy (IgAN) was the most frequently diagnosed GD (20%), aligning with frequencies reported in European registries. Diabetic glomerular nephropathy was the most common secondary GD (10%). It also presented the highest median renal histopathological prognostic score (2), indicating a poorer prognosis. Lower eGFR and higher proteinuria were independently associated with higher scores. This decade-long study highlights IgAN as the most frequent GD diagnosed by KB. Diabetic glomerular nephropathy was identified as the most common secondary GD. The renal histopathological prognostic score, notably high in diabetic glomerular nephropathy patients, was correlated with lower eGFR and higher proteinuria, underlining its clinical relevance.

Peritoneal Dialysis-Induced Encapsulating Peritonitis: Diagnostic and Therapeutic Challenges in Women with Benign Gynecological Pathology.

Background: Peritoneal sclerosis (PS) and its most severe form, encapsulating PS (EPS), are rare entities that can occur in various procedures (liver transplantation, intraperitoneal chemotherapy) or secondary to medications (beta-blockers); however, PS or EPS typically occur in patients undergoing peritoneal dialysis as a form of renal function substitution. Medical or surgical treatments can be applied, but morbidity and mortality have high rates. This condition typically presents clinically as an intestinal obstruction caused by the inclusion of the intestinal loops in the peritoneal fibrous membrane. Methods: Herein, we present data from a single tertiary surgery center that has dedicated teams for patients receiving dialysis. Over 12 years, we analyzed a group of 63 patients admitted for catheter replacement/removal or for acute surgical pathology. In five cases (7.9%), we diagnosed EPS. Two patients with EPS presented with atypical abdominal pathologies requiring emergency surgery: one case of hemoperitoneum caused by a ruptured ovarian cyst and one case of uterine fibroids and metrorrhagia. Results: The definitive diagnoses were established intraoperatively and by analyzing the morpho-pathological changes in the peritoneum. The possible intraoperative challenges included laborious dissection, difficulties in restoring the correct anatomical landmarks, an increased duration of the surgical intervention and a high rate of incidents and accidents. Conclusions: The aim of the present study was to emphasize the possibility of other surgical pathologies overlapping with EPS, increasing the complexity of the surgical intervention.

Mortality in IgA Nephropathy: A Long-Term Follow-Up of an Eastern European Cohort.

Background and Objectives: IgA nephropathy (IgAN), the most common primary glomerulonephritis, has been extensively studied for renal outcomes, with limited data on patient survival, particularly in Eastern Europe. We aimed to investigate the long-term survival rate of patients with IgAN and the associated risk factors in an Eastern European cohort. Materials and Methods: We conducted a retrospective analysis of 215 IgAN patients (median age 44, 71% male) diagnosed at a Romanian tertiary center between 2010 and 2017. We assessed clinical and pathological attributes, including the Charlson comorbidity index, the prevalence of diabetes, renal function, and treatment with renin-angiotensin-system inhibitors (RASIs). Results: Over a median 7.3-year follow-up, 20% of patients died, mostly due to cardiovascular diseases. Survival rates at 1, 5, and 10 years were 93%, 84%, and 77%, respectively. Deceased patients had higher Charlson comorbidity index scores, greater prevalence of diabetes, and poorer renal function. They were less frequently treated with RASIs and more frequently reached end-stage kidney disease (ESKD). Conclusions: We report a 20% mortality rate in our Eastern European IgAN cohort, primarily due to cardiovascular diseases. Death correlates with increased age, comorbidity burden, decreased renal function at diagnosis, and the absence of RASI use. RASI treatment may potentially improve survival, highlighting its importance in managing 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.

Glasgow prognostic score as an outcome predictor for patients initiating hemodialysis.

INTRODUCTION: This retrospective study examined the relationship between the Glasgow Prognostic Score (GPS) at hemodialysis (HD) initiation and overall/cardiovascular mortality. METHODS: A total of 264 patients starting HD between 2014 and 2015 at a single center were studied. Follow-up persisted until therapy change, death, or study end (December 31, 2021), with a median of 6.8 years. RESULTS: Patients with a higher GPS more frequently had emergent HD initiation and showed increased eGFR at initiation. During follow-up, 60% of patients died, with cardiovascular disease being the leading cause. Univariate analysis revealed a significant difference in median survival time across GPS classes. Cox proportional hazard models confirmed a significant association between GPS and mortality. CONCLUSIONS: We report a significant association between GPS at HD initiation and mortality. GPS may prove useful as a prognostic tool for identifying high-risk patients, underscoring the need for future research to validate these findings and explore the potential of GPS-based interventions.

Lupus nephritis with cryoglobulinemic glomerulonephritis features: a diagnostic conundrum.

In this clinical case, we report an atypical and unique presentation of systemic lupus erythematosus (SLE) in a 39-year-old female with nephrotic syndrome. The patient exhibited class IV plus V lupus nephritis and extensive immune complex deposition within the intracapillary and arteriolar regions suggestive of cryoglobulinemic glomerulonephritis, despite no detectable circulating cryoglobulins. Electron microscopy revealed cryoglobulin-like deposit distribution in all glomerular examined compartments, namely subendothelial, intramembranous, subepithelial, and mesangial, apparently extending from the capillary hyaline thrombi. The case highlights the possibility of severe renal injury in SLE without circulating cryoglobulins and the diverse kidney manifestations associated with the disease. However, the impact on patient outcome was minimal, as classical treatment (id est National Institute of Health regimen) remained effective.

Prognostic role of glomerular electron microscopy lesions in IgA nephropathy: "the devil is in the details".

INTRODUCTION: Transmission electron microscopy enables examination of ultrastructural glomerular changes; while this tool has already been applied in IgA nephropathy (IgAN), limited information exists on the prognostic value in this disease. We aimed to systematically investigate ultrastructural lesions and assess their role in predicting the evolution of IgA nephropathy to end-stage kidney disease. METHODS: A single-center retrospective study was performed on 107 consecutive IgAN patients (median age 42 years, 67% male, estimated glomerular filtration rate 46 mL/min, proteinuria 1.0 g/g) between 2010 and 2015, who were followed-up until end-stage kidney disease, death, or end of study (January 2021). A pathologist evaluated the Mesangial hypercellularity (M), Endocapillary hypercellularity (E), Segmental glomerulosclerosis (S), and Tubular atrophy/interstitial fibrosis-Crescents (C) (MEST-C) score and transmission electron microscopy lesions according to a comprehensive protocol that encompassed all glomerular structures. RESULTS: Patients were followed up for a median of 7.1 years; 32 (43%) reached end-stage kidney disease. Patients who reached kidney failure had higher comorbidity score, more frequent arterial hypertension, lower estimated glomerular filtration rate, and higher MEST-C score. In terms of transmission electron microscopy lesions, patients who progressed to end-stage kidney disease had more frequent podocyte activation, effacement, and presence of microvilli; more frequent signs of endothelial cell activation and fenestration; higher mesangial cell proliferation. In the univariate Cox proportional hazard regression, higher MEST-C score and lesions detected by transmission electron microscopy in podocytes, endothelial cells, and mesangial cell proliferation were associated with shorter kidney survival time. In the multivariate Cox proportional hazard regression, only higher MEST-C score, presence of podocytes with microvilli, and mesangial cell proliferation were associated with end-stage kidney disease. CONCLUSION: This study shows that, besides the MEST-C score, the presence of podocytes with microvilli and mesangial cell proliferation are associated with poor kidney survival in IgAN patients, highlighting the prognostic value of lesions detected by transmission electron microscopy.

Multiple Myeloma and Kidney Impairment at Diagnosis: A Nephrological Perspective from an Eastern European Country.

Background and Objectives: The clinical presentation and survival factors in patients with myeloma-related kidney impairment (MRKI) at diagnosis remain a topic of ongoing research, given the complex interplay between nephrology and hematology. To date, no studies have specifically reported outcomes for these patients in Eastern Europe. Materials and Methods: We conducted a retrospective, unicentric study of consecutive newly diagnosed patients with MRKI in our tertiary nephrology service in Romania between 2015 and 2020; follow-up extended until 1 September 2022, covering a study period of 90 months. Results: We identified 89 consecutive patients with MRKI (median age 66 years, 38% male, median eGFR 5 mL/min). The majority of patients had arterial hypertension (71%) and systemic atherosclerosis (58%), and the most frequent clinical features at presentation were asthenia (75%) and bone pain (51%). Light-chain-restricted myeloma was the most common type (55%), with kappa free light chain being more frequent (53%). Among the patients, 81% presented with acute kidney injury (AKI), and 38% required hemodialysis at diagnosis. During the study period, 65% of the patients died, and hypoalbuminemia and the need for hemodialysis at diagnosis were significantly associated with mortality in multivariate analysis. Conclusions: Patients with MRKI who present to the nephrologist more frequently exhibit light chain restriction and most often present with AKI, with one-third requiring hemodialysis at diagnosis. Moreover, hypoalbuminemia and the initiation of hemodialysis at diagnosis were significantly associated with increased mortality.

Anti-phospholipase A2 receptor positive membranous nephropathy: investigating the link between electron microscopy stages and clinical outcome.

This retrospective, observational study sought to examine the relationship between Ehrenreich-Churg electron microscopy (EM) stages and long-term outcomes in anti-PLA2R membranous nephropathy (MN). Seventy-one patients with anti-PLA2R MN (median titer 185.7RU/mL) were followed for a median of 46 months, with end-stage kidney disease (ESKD) as the primary endpoint, and response to treatment as a secondary endpoint. Patients were grouped into stages I-II (41 patients) and stages III-IV (30 patients) for analytical purposes. Notably, the III-IV group demonstrated a lower eGFR, lower anti-PLA2R titer, but a higher chronicity score. Kaplan-Meier analysis showed shorter mean kidney survival time in stages III-IV compared to I-II (p 0.03). However, multivariate analysis using Cox regression indicated that Ehrenreich-Churg stages did not significantly influence kidney survival, but lower eGFR at diagnosis and higher histopathological chronicity score did. Remission was achieved by 64% of patients and no relationship between Ehrenreich-Churg stages and treatment response was found. The only identified risk factor for not achieving remission was the severity of hyposerinemia at diagnosis. In conclusion, while EM stages III-IV are associated with more chronic lesions and stages I-II with more active immunologic disease, the histological chronicity score seems to be a stronger predictor of long-term outcomes.

Nephrotic Syndrome and Statin Therapy: An Outcome Analysis.

Background and Objectives: Hypercholesterolemia in patients with nephrotic syndrome (NS) may predispose to cardiovascular events and alter kidney function. We aimed to evaluate statins efficiency in NS patients under immunosuppression using four endpoints: remission rate (RR), end-stage kidney disease (ESKD), major cardiovascular events (MACE), and thrombotic complications (VTE). Materials and Methods: We retrospectively examined the outcome at 24 months after diagnosis of 154 NS patients (age 53 (39-64) years, 64% male, estimated glomerular filtration rate (eGFR) 61.9 (45.2-81.0) mL/min). During the follow-up, the lipid profile was evaluated at 6 months and at 1 and 2 years. Results: The median cholesterol level was 319 mg/dL, and 83% of the patients received statins. Patients without statins (17%) had similar age, body mass index, comorbidities, blood lipids levels, NS severity, and kidney function. The most used statin was simvastatin (41%), followed by rosuvastatin (32%) and atorvastatin (27%). Overall, 79% of the patients reached a form of remission, 5% reached ESKD, 8% suffered MACE, and 11% had VTE. The mean time to VTE was longer in the statin group (22.6 (95%CI 21.7, 23.6) versus 20.0 (95%CI 16.5, 23.5) months, p 0.02). In multivariate analysis, statin therapy was not associated with better RR, kidney survival, or fewer MACE; however, the rate of VTE was lower in patients on statins (HR 2.83 (95%CI 1.02, 7.84)). Conclusions: Statins did not improve the remission rate and did not reduce the risk of MACE or ESKD in non-diabetic nephrotic patients. However, statins seemed to reduce the risk of VTE. Further randomized controlled studies are needed to establish statins' role in NS management.

Budd-Chiari syndrome: An unusual complication of an internal jugular tunneled dialysis catheter.

Budd-Chiari syndrome due to the tip of an internal jugular tunneled dialysis catheter malposition in inferior vena cava or hepatic vein is a rare complication. We aimed to present our experience and compare it with the previous reports to highlight the clinical features and the optimal management. A 57-year-old female with history of ANCAp vasculitis, treated by hemodialysis in the last 2 years on a right internal jugular vein tunneled catheter was admitted for pain in the right upper quadrant. A subacute Budd-Chiari syndrome due to catheter malposition was diagnosed. The catheter was removed, and a new tunneled hemodialysis line was inserted in the right internal jugular vein with the tip at the junction of right atrium with superior vena cava. Anticoagulation with apixaban 2.5 mg twice daily was started after catheter replacement and the patient was discharged. At 1 month follow-up the patient had no symptoms, and the ultrasound revealed the absence of the thrombus in the inferior vena cava. Imagining monitoring for malposition after insertion or in a clinical context suggestive for Budd-Chiari syndrome is essential for early diagnosis and treatment. In our case, anticoagulation with apixaban and prompt catheter replacement resulted in Budd-Chiari syndrome resolution.

How useful is kidney biopsy for the management of glomerulopathies in the elderly?

BACKGROUND: The use of kidney biopsy in elderly individuals is still matter of discussion. The purpose of this study is to assess the utility of kidney biopsy for the management of glomerulopathies in an Eastern European cohort, targeting patients older than 65 years. METHODS: This retrospective study included 875 adults (147 older than 65 years), with biopsy-proven glomerulopathies, followed up for 71.1 (95% CI 68.2-73.9) months. The primary endpoint was chronic renal replacement therapy initiation. Statistical evaluation was performed with IBM SPSS software version 20, Analyse-it, and SAS Studio. The Kaplan-Meier method was used to estimate the time to death and the log-rank test was used for comparisons. The multivariate Cox proportional hazard analysis was used to evaluate the risk of death. RESULTS: Secondary glomerulopathies were more frequent in patients aged > 65 years (52.4% vs. 41.9%, p = 0.004). Membranous nephropathy and amyloidosis were the most frequent primary and secondary glomerulopathies in this age group. Kidney biopsy complications were low (< 4%) in both age groups. In 42% of the elderly, the result of biopsy guided the immunosuppressive therapy. While the all-cause mortality rate was higher (OR 4.2; 95% CI 2.7-6.7; p < 0.0001) in elderly individuals, the rate of renal replacement therapy initiation was similar (31.3 vs 26%; p = 0.1) in both age groups. In the competitive risk analysis, kidney survival was similar irrespective of age [CIF 0.4 (95% CI 0.26-0.53) vs. 0.34 (95% CI 0.28-0.39), p = 0.08]. However, after adjusting for the confounding factors, younger age was associated with an increased risk of renal replacement therapy (HR = 1.57, p = 0.01), along with secondary glomerulopathies. CONCLUSION: The diagnosis of an underlying glomerulopathy guided the therapy in almost one-half of the elderly patients who underwent a kidney biopsy, provided important prognostic information and had a low complications rate; kidney biopsy may therefore be considered a safe, reliable procedure in the management of glomerulopathies, even in patients over 65 years of age.

Immunosuppressive therapy versus supportive care in IgA nephropathy patients with stage 3 and 4 chronic kidney disease.

The use of immunosuppressive therapy for immunoglobulin A nephropathy (IgAN) patients with stage 3 or 4 chronic kidney disease (CKD) is controversial. We performed a monocentric retrospective study on 83 consecutive IgAN patients with stage 3 or 4 CKD and proteinuria ≥0.75 g/d (age 41 [33-56] years, 72% male, estimated glomerular filtration rate 36.1 [25.4-47.5] mL/min/1.73 m2) who received uncontrolled supportive care (Supp) (n = 36), corticosteroids/corticotherapy (CS) (n = 14), or CS combined with monthly pulses of cyclophosphamide (CS + CFM) (n = 33) between 2010 and 2017. Patients were followed until composite endpoint (doubling of serum creatinine, end-stage kidney disease (dialysis or kidney transplant) or death, whichever came first) or end of study (January 2020). Patients were followed for a median of 29 (95% confidence interval = 25.2-32.7) months, and 12 (15%) patients experienced the composite endpoint. Within the limitation of a retrospective study, our results suggest no benefit from immunosuppressive therapy in patients with IgAN with stage 3 and 4 CKD as compared with supportive care. There were no differences between the 3 studied groups regarding age, estimated glomerular filtration rate, proteinuria, Oxford classification score, arterial hypertension, and therapy with renin-angiotensin system inhibitors. Mean kidney survival time for the entire cohort was 81.0 (95% confidence interval = 73.1-89.0) months, without significant differences between the 3 groups. In univariate and multivariate Cox regression analysis adjusted for IgAN progression factors, immunosuppressive therapy was not associated with better kidney survival when compared with supportive therapy.

Negative anti-phospholipase A2 receptor antibody status at three months predicts remission in primary membranous nephropathy.

BACKGROUND: The value of anti-phospholipase A2 receptor antibody (anti-PLA2R ab) monitoring at 3 months after diagnosis in membranous nephropathy (MN) remains uncertain. METHODS: We retrospectively examined the outcome on 1 August 2020 of 59 adult patients (age 54 (44, 68) years, 69% male, SCr 1.0 (0.9, 1.3) mg/dL) diagnosed with MN (kidney biopsy, positive serum anti-PLA2R ab). The outcomes were: kidney survival; partial and/or complete remission. RESULTS: Most of the studied patients (97%) received immunosuppression, cyclophosphamide regimens were the most frequent (87%), followed by cyclosporine (10%). The median time to remission was 12.0 months and the cumulative remission rates were 34% at 6, 54% at 12, and 73% at 24 months. Forty (69%) patients had negative anti-PLA2R ab at 3 months, they had similar age, serum creatinine, albumin, proteinuria, and treatment with the group with positive ab at 3 months. In the Cox proportional hazard model, three months anti-PLA2R ab negativization (HR 0.4 (95%CI 0.1, 0.9)) was an independent predictor for remission, while baseline hypoalbuminemia (HR 3.0 (95%CI 1.5, 5.7)) was associated with absence of remission. Six (10%) patients died, mostly due to cardiovascular disease and infections. A total of five (9%) patients started dialysis. Mean kidney survival time was 50.3 months and there was no survival difference in relation to baseline anti-PLA2R ab titer (p .09) or 3 months negativization (p .8). CONCLUSIONS: Three months anti-PLA2R ab negativization seems to be a late predictor of remission, and lower serum albumin at diagnosis is an early marker for remission absence. Abbreviations: anti-P LA2R ab, anti-phospholipase A2 receptor antibody; eGFR, estimated glomerular filtration rate; ESKD, end stage kidney disease; MN, membranous nephropathy; NELL-1, neural epidermal growth factor-like 1 protein; RAAS: renin-angiotensin-aldosterone system; RBC: red blood cells; RRT, renal replacement therapy; T HSD7A, thrombospondin type-1 domain containing 7A.

Inflammation-based modified Glasgow prognostic score and renal outcome in chronic kidney disease patients: is there a relationship?

BACKGROUND: Chronic kidney disease (CKD) progression is presumably related to inflammatory response. The modified Glasgow prognostic score (mGPS), based on a combination of albumin and C-reactive protein, has been derived from oncology and validated in multiple diseases. AIMS: To evaluate the relationship between the mGPS and CKD progression. METHODS: The present retrospective unicentric cohort study included 547 CKD patients (age 60.2 years; 53% male; estimated glomerular filtration (eGFR) 42.0 mL/min; mean change -2 mL/min/year) admitted between 1 January 2007 and 31 December 2012. Patients' records were reviewed from the CKD diagnosis to one of the four outcomes: end-stage kidney disease (ESKD), death, loss to follow up or until 31 July 2017. RESULTS: The mGPS score was 0 for 420 (78%), 1 for 110 (19%) and 2 for 17 (3%) patients. More patients with rapid CKD progression were found in the group with the highest mGPS (P = 0.05). mGPS was negatively correlated with baseline eGFR and positively with albuminuria. In the multivariate analysis, mGPS was associated with the eGFR slope. During the study period, 130 (24%) patients died and 109 (20%) reached ESKD. The mean kidney survival time was 8.1 (95% confidence interval 7.9-8.4) years. Patients with zero mGPS had better kidney survival than those with the score of 1 and 2 (Kaplan-Meier, P = 0.02). However, the kidney survival differences were not present after adjusting for CKD progression risk factors. CONCLUSION: The inflammation-based mGPS score was associated with eGFR decline in CKD patients. Therefore, could prove useful in improving risk stratification of CKD patients.