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Contains fulltext : 232930.pdf (Publisher’s version ) (Closed access) BACKGROUND: On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. METHODS: In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to

Background On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. Methods In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a $25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to,1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR). Results During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups. Conclusions Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints. Copyright © 2021 by the American Society of Nephrology.

Background and objectives Shared decision making in patients with glomerular disease remains challenging because outcomes important to patients remain largely unknown. We aimed to identify and prioritize outcomes important to patients and caregivers and to describe reasons for their choices. Design, setting, participants, & measurements We purposively sampled adult patients with glomerular disease and their caregivers from Australia, Hong Kong, the United Kingdom, and the United States. Participants identified, discussed, and ranked outcomes in focus groups using the nominal group technique; a relative importance score (between zero and one) was calculated. Qualitative data were analyzed thematically. Results Across 16 focus groups, 134 participants (range, 19–85 years old; 51%women), including 101 patients and 33 caregivers, identified 58 outcomes. The ten highest-ranked out comes were kidney function(importance score of 0.42), mortality (0.29), need for dialysis or transplant (0.22), life participation (0.18), fatigue (0.17), anxiety (0.13), family impact (0.12), infection and immunity (0.12), ability to work (0.11), and BP (0.11). Three themes explained the reasons for these rankings: Constraining day-to-day experience, impaired agency and control over health, and threats to future health and family. Conclusions Patients with glomerular disease and their caregivers highly prioritize kidney health and survival, but they also prioritize life participation, fatigue, anxiety, and family impact. © 2020 by the American Society of Nephrology.

ImportanceAlthough IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. ObjectiveTo derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and ParticipantsWe derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and MeasuresCox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R-D(2) measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. ResultsThe study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R-D(2) (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (Delta C, 0.04; 95% CI, 0.03-0.04 and Delta C, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R-D(2) (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. Conclusions and RelevanceIn this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

ImportanceAlthough IgA nephropathy (IgAN) is the most common glomerulonephritis in the world, there is no validated tool to predict disease progression. This limits patient-specific risk stratification and treatment decisions, clinical trial recruitment, and biomarker validation. ObjectiveTo derive and externally validate a prediction model for disease progression in IgAN that can be applied at the time of kidney biopsy in multiple ethnic groups worldwide. Design, Setting, and ParticipantsWe derived and externally validated a prediction model using clinical and histologic risk factors that are readily available in clinical practice. Large, multi-ethnic cohorts of adults with biopsy-proven IgAN were included from Europe, North America, China, and Japan. Main Outcomes and MeasuresCox proportional hazards models were used to analyze the risk of a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease, and were evaluated using the R-D(2) measure, Akaike information criterion (AIC), C statistic, continuous net reclassification improvement (NRI), integrated discrimination improvement (IDI), and calibration plots. ResultsThe study included 3927 patients; mean age, 35.4 (interquartile range, 28.0-45.4) years; and 2173 (55.3%) were men. The following prediction models were created in a derivation cohort of 2781 patients: a clinical model that included eGFR, blood pressure, and proteinuria at biopsy; and 2 full models that also contained the MEST histologic score, age, medication use, and either racial/ethnic characteristics (white, Japanese, or Chinese) or no racial/ethnic characteristics, to allow application in other ethnic groups. Compared with the clinical model, the full models with and without race/ethnicity had better R-D(2) (26.3% and 25.3%, respectively, vs 20.3%) and AIC (6338 and 6379, respectively, vs 6485), significant increases in C statistic from 0.78 to 0.82 and 0.81, respectively (Delta C, 0.04; 95% CI, 0.03-0.04 and Delta C, 0.03; 95% CI, 0.02-0.03, respectively), and significant improvement in reclassification as assessed by the NRI (0.18; 95% CI, 0.07-0.29 and 0.51; 95% CI, 0.39-0.62, respectively) and IDI (0.07; 95% CI, 0.06-0.08 and 0.06; 95% CI, 0.05-0.06, respectively). External validation was performed in a cohort of 1146 patients. For both full models, the C statistics (0.82; 95% CI, 0.81-0.83 with race/ethnicity; 0.81; 95% CI, 0.80-0.82 without race/ethnicity) and R-D(2) (both 35.3%) were similar or better than in the validation cohort, with excellent calibration. Conclusions and RelevanceIn this study, the 2 full prediction models were shown to be accurate and validated methods for predicting disease progression and patient risk stratification in IgAN in multi-ethnic cohorts, with additional applications to clinical trial design and biomarker research.

Glomerular diseases are one of the most frequent causes of chronic kidney disease, focal and segmental glomerulosclerosis being one of the commonest glomerulopathies. However, the etiology of this glomerular entity, which merely depicts a morphologic pattern of disease, is often not established and, in most of the patients, remains unknown. Nephrologists tend to assume focal and segmental glomerulosclerosis as a definitive diagnosis. However, despite the increasing knowledge developed in the field, genetic causes of glomerular diseases are currently identified in fewer than 10% of chronic kidney disease subjects. Moreover, unexplained familial clustering among dialysis patients suggests that genetic causes may be underrecognized. Secondary focal and segmental glomerulosclerosis due to genetic mutations mainly located in the podocyte and slit diaphragm can occur from childbirth to adulthood with different clinical presentations, ranging from mild proteinuria and normal renal function to nephrotic syndrome and renal failure. However, this histopathological pattern can also be due to primary defects outside the glomerulus. The present report illustrates an adult case of secondary focal and segmental glomerulosclerosis with a dominant tubulointerstitial damage that led to the pursue of its cause at the tubular level. In this patient with an undiagnosed family history of adult kidney disease, a genetic study unraveled a mutation in the mucin-1 gene and a final diagnosis of adult dominant tubular kidney disease-MUC1 was made.

IgA nephropathy is the most frequent cause of primary glomerulonephritis, portends erratic patterns of clinical presentation, and lacks specific treatment. In general, it slowly progresses to end-stage renal disease. The clinical course and the response to therapy are usually assessed with proteinuria and serum creatinine. Validated biomarkers have not been identified yet. In this report, we present a case of acute renal injury with proteinuria and microscopic hematuria in a young male. A kidney biopsy disclosed IgA nephropathy. Podocyturia was significantly elevated compared to normal subjects. Proteinuria, renal function, and podocyturia improved promptly after steroids and these variables remained normal after one year of follow-up, when steroids had already been discontinued and patient continued on valsartan and amiloride. Our report demonstrates that podocyturia is critically elevated during an acute episode of IgA nephropathy, and its occurrence may explain the grim long-term prognosis of this entity. Whether podocyturia could be employed in IgA nephropathy as a trustable biomarker for treatment assessment or even for early diagnosis of IgA nephropathy relapses should be further investigated.

No specific or efficient treatment exists for Alport syndrome, an X-linked hereditary disease caused by mutations in collagen type IV, a crucial component of the glomerular basement membrane. Kidney failure is usually a major complication of the disease, and patients require renal replacement therapy early in life. Microhematuria and subsequently proteinuria are hallmarks of kidney involvement, which are due to primary basement membrane alterations that mainly cause endothelial thrombosis and podocyte contraction and ulterior irreversible detachment. Commonly drug-based approaches include angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which are employed to reduce proteinuria and thus retard kidney disease progression and cardiovascular morbidity and mortality. However, as any hereditary disease, it is expressed as early as in the intrauterine life, and usually an index case is helpful to detect family-related cases. As no specific treatment exists, pathophysiologically based approaches are useful. The present case illustrates the reduction rate of urinary podocyte loss and proteinuria after amiloride administration and suggests the molecular pathways involved in Alport renal disease. Finally, podocyturia rather than proteinuria should be considered as an earlier biomarker of kidney involvement and disease progression in Alport disease.

The time for starting a patient with Fabry disease on enzyme replacement therapy is still a matter of debate, particularly when no overt classical clinical signs or symptoms are present. With respect to Fabry nephropathy, a dual problem coexists: the reluctance of many nephrologists to start enzyme replacement infusion until signs of renal disease appear as the appearance of proteinuria or an elevation in serum creatinine and the lack of validated biomarkers of early renal damage. In this regard, proteinuria is nowadays considered as an early and appropriate marker of kidney disease and of cardiovascular morbidity and mortality. However, in this report we demonstrate that podocyturia antedates the classical appearance of proteinuria and could be considered as an even earlier biomarker of kidney damage. Podocyturia may be a novel indication for the initiation of therapy in Fabry disease.

Patients with Fabry disease present a higher risk of cardiovascular and kidney morbidity. We present a patient with a past history of biopsy-proven Fabry disease and stage 3 chronic kidney disease. Proteinuria partially dropped from 6.8 g/day to 2.1 g/day despite an aggressive regime which consisted of low-salt diet, agalsidase beta infusions, dual blockade of the renin-angiotensin system, and low-dose maintenance of steroids. As proteinuria is considered a risk marker of cardiovascular disease and of progression of kidney disease, we added amiloride 5 mg/day, a drug with proven effects in podocyte stabilization and proteinuria actions at the distal convoluted tubule. Proteinuria finally decreased to 0.8 g/day. This report highlights the relevance of intervening on proteinuria in a multitarget approach in order to reduce it as much as possible. Due to this pharmacological response, we suggest that although agalsidase beta specific treatment protects the endothelium, the podocyte, and the tubule in Fabry disease and secondary haemodynamic and immunologic pathways are treated with inhibition of the renin-angiotensin system and steroids, amiloride may act as a complementary tool in podocyte stabilization and in proteinuria effects at the distal tubule.

Los pacientes con mieloma múltiple (MM) raramente presentan ascitis. La misma puede responder a diversos mecanismos, siendo las causas más frecuentes el aumento de permeabilidad del peritoneo y la hipertensión portal por infiltración hepática. La ascitis mielomatosa (AM) ocurre con más frecuencia en pacientes con paraproteína de tipo Ig-G e Ig-A y su pronóstico es sombrío. Se presenta el caso de una paciente de sexo femenino de 50 años con diagnóstico de MM IgA-kappa que evoluciona con insuficiencia cardíaca (IC), leucemia de células plasmáticas y ascitis de causa mixta, por infiltración peritoneal por células mielomatosas, compromiso hepático e IC. Se realiza una revisión de las distintas causas de ascitis en pacientes con MM. Asimismo se resumen todos los casos publicados en la literatura mundial de AM. Nuestro reporte representa el primer caso de AM en un paciente con leucemia de células plasmáticas. Ascites is rare in patients with multiple myeloma (MM). It may be due to diverse mechanisms, most frequently because of an increased permeability of the peritoneum or because of portal hypertension due to liver infiltration. Myelomatous ascites occurs more frequently in patients having Ig-G or Ig-A paraprotein and their prognosis is poor. It is submitted the case of a female patient aged 50 years with IgA-kappa MM, who evolved with cardiac failure (CF), plasma cells leukemia and ascites of mixed cause, because of peritoneal infiltrate of myelomatous cells, hepatic compromise and CF. A review of the different causes of ascites in patients with MM is performed. There are also summarized all myelomatous ascites cases published in the literature. Our report presents the first case of myelomatous ascites in a patient with plasma cells leukemia.

La sudoración nocturna ha sido definida como la presencia reiterada de sudoración durante el sueño que obliga a cambiar la ropa de cama. En estudios dirigidos este signo es muy variable, presentándose en un 30 % de los pacientes no obstétricos y hasta en un 60 % de las mujeres embarazadas. Las causas son diversas: infecciones, tumores, medicamentos, alteraciones endocrinológicas, ataques de pánico y misceláneas, por lo que cada paciente con sudoración nocturna se convierte en un desafío diagnóstico. Presentamos dos pacientes con sudoración nocturna y a quienes luego de numerosos estudios, se les diagnóstica reflujo gastroesofágico, presentando excelente respuesta y desaparición de la sudoración con el tratamiento anti reflujo. Esta presentación, junto con una revisión de la literatura pretende resaltar la importancia de considerar el reflujo gastroesófagico en el algoritmo diagnóstico de los pacientes con sudoración nocturna, una vez excluidos los procesos potencialmente graves. Night sweats has been defined as drenching sweats that require the patient to change bedclothes. In current studies night sweats appear in 30% of non-obstetric patients and affects approximately 60% of pregnant women. Differential diagnoses include infections, malignancy, medications, hot flashes and panic attacks, making of each patient a challenge. We present two patients with night sweating. After excluding systemic diseases the diagnosis of gastroesophageal reflux was made, with excellent response to anti-reflux treatment. The presentation of our two patients coupled with a deep literature review, underscores the importance of gastroesophageal reflux as a cause of night sweating.