Background and Aims As we age, we lose kidney function and accumulate risk factors and comorbidities that predispose to kidney damage. However, kidney disease can develop at any time. Life expectancy continues to improve worldwide. For that reason, more elderly patients are undergoing diagnostic kidney biopsies (KB). There is a general reluctance in performing KB in those patients. It is important to know if a diagnosis KB in elderly patients can have a positive therapeutic impact. Method In this retrospective cohort study, we analyzed the medical charts of all patients aged ≥ 80years who underwent a native kidney biopsy (KB) between January and December 2021, in a central hospital in Portugal. Results Between January and December 2021, 59 patients underwent a native KB, 6 of them over 80 years of age (10% of all patients). Between those elderly patients, the median age was 82 years. The indications for KB were chronic kidney disease with a nephrotic range proteinuria in 3 patients, nephrotic syndrome, acute glomerulonephritis and acute kidney injury in 1 patient each. Median serum creatinine was 2.27 mg/dL (minimum 0.8 and maximum 5.4 mg/dL) and median protein-to-creatinine ratio was 5.7g/g (minimum 3.3 and maximum 13g/g). The pathological diagnoses found were focal and segmental glomerulosclerosis (FSGS) (n=2), pauci-immune crescentic glomerulonephritis (n=1), membranous nephropathy in a patient with a follicular lymphoma (n=1), acute interstitial nephritis (AIN) (n=1), and diabetic glomerulosclerosis in a patient with a monoclonal gammopathy of undetermined significance (n=1). 3 patients have received a kidney-specific treatment – the patient with AIN started corticosteroids, one patient with FSGS was submitted to corticosteroids plus tacrolimus, and the patient with pauci-imune crescentic glomerulonephritis to corticosteroids plus rituximab. The patient with membranous nephropathy and follicular lymphoma received a specific chemotherapy regimen according with lymphoproliferative disease. An improvement in kidney function occurred only in one patient and the other three developed adverse effects (particularly corticosteroids induced diabetes and infections). One year later, one of patients who received treatment was dead, another one was on hemodialysis, and the other two patients had a glomerular filtration rate lower than 15mL/min/1.73 m2. Conclusion Elderly patients have a higher risk of adverse effects from the kidney-specific treatment. It is important to assess the therapeutic risk/benefit when considering performing a renal biopsy in these patients.
Background and Aims SGLT2 inhibitors (SGLT2i) have a beneficial effect in diabetic and non-diabetic proteinuric chronic kidney disease (CKD), demonstrated in large randomized controlled trials. However, there is limited information about real life experience with SGLT2i in non-diabetic CKD like IgA nephropathy (IgAN). Method All patients with biopsy-proven IgA nephropathy since 2015 were evaluated for SGLT2i use. We collected data on age, gender, the use of renin-angiotension-aldosterone system inhibitors (RAASi), eGFR, glycosuria and proteinuria at baseline, at 6 months and at one year of follow-up. Glomerular filtration rate (eGFR) was estimated using the CKD-EPI equation. Data was analyzed using Jamovi®. Results 51 patients had IgAN diagnosed by kidney biopsy from April 2015 until March 2021. Eleven of these started SGLT2i between December 2020 and February 2022 (at their physician's description). Their median age was 52, nine were male and all were taking RAASi. The initial median proteinuria was 1 g/g (range 0.5-2.0 g/g), median eGFR was 57.5 mL/min (range 16.8-104 mL/min). At 6 months, the median proteinuria was 0.7 g/g (range 0.8-4.8 g/g), median eGFR was 42.6 mL/min (range 13.9-108 mL/min). One year after beginning SGLT2i, 8 patients have laboratory values and the median value of proteinuria was 0.85 g/g (range 0.2-3.0 g/g) and the median eGFR was 40.5 mL/min (range 14.5-85.4 mL/min). All patients had glycosuria at all urine evaluations confirming no discontinuations of the SGLT2i. No serious adverse events were reported and none of the patients needed dialysis or died. There were no significant differences between proteinuria and eGFR between evaluations at the start, 6 months and 1 year of follow-up. Conclusion SGLT2i have become important drugs in IgAN. Our first cases who started SGLT2i showed good compliance (using glycosuria as an indirect tool to monitor adherence) and no adverse events, irrespective of their initial eGFR. The small sample was probably a limitation to the lack of significant results.
Background and Aims SARS-CoV-2 represents a challenge for hemodialysis (HD) patients due to their multiple comorbidities, disturbed immune defenses in the setting of kidney disease and increased age. Furthermore, sharing collective spaces during HD sessions increases the risk of contamination. In March 2020, the first COVID-19 cases in Portugal occurred in Felgueiras, a municipality belonging to the district of Porto. The HD unit that serves this population has 69 in-center patients and, from March 2020 until January 2021, has had 14 COVID-19 cases. We describe our experience concerning patient management and their clinical characteristics. Method Clinical and laboratory data were collected. We aimed at assessing the impact of the infection in hemoglobin, alanine transaminase, several electrolytes - potassium, phosphorus, sodium and calcium - as well as the normalized protein catabolic rate (nPCR) comparing results from the month before infection with those of the month after cure. Statistical analysis used SPSS® and variables were compared using paired-samples t-test. Results We used a dedicated room and staff for COVID-19 patients, disinfection protocols and specific routes. Transportation was done with a maximum of 3 patients in a 9-seater vehicle, all patients used masks, practiced social distancing, were asked for symptoms and had their temperature measured on each HD session. SARS-CoV-2 infection was established by reverse transcription polymerase chain reaction on nasal and oropharyngeal swabs. Of the 14 cases, 3 occurred in March, 5 from October until Christmas and 6 from then onwards, accounting for approximately 20% of the unit’s patients. Of these, 2 were asymptomatic, 6 had predominantly respiratory symptoms, 1 had fever and 1 had gastrointestinal symptoms. Three were hospitalized, 2 died due to COVID-19 and 1 died 1 month after cure due to advanced cancer. Mean age of these patients was 70±13.2; 5 were females and 6 had diabetic nephropathy. Only 7 patients had post-COVID-19 results for comparison. The mean hemoglobin value before COVID-19 was 10.5±1.7g/dL and did not change significantly after COVID-19. Although phosphorous dropped from a mean 3.8±0.9mg/dL to 3.2±1.3mg/dL, this difference did not reach significance (p=0.43). All other electrolytes remained stable. nPCR dropped from 1.23±0.47 to 0.95±0.37 although not a significant difference (p=0.24). Five patients were tested for IgG/IgM antibodies against SARS-CoV-2 one month after cure using Elecsys® qualitative immunoassay and 4 tested positive. Conclusion COVID-19 is a problem for HD patients where the percent of cases is larger than in the general population. Our 3 first cases and the 4 last cases shared the same HD shift and occurred in the same period confirming that, despite all protective measures, sharing the facilities in close proximity is a risk factor. Respiratory symptoms predominated but were only severe requiring hospital admission in 3 patients. Mortality represented 14% and the 2 patients whose death was attributable to COVID-19 had an increased burden of comorbidities and were old. Seroconversion was high 1 month after the disease. The only patient who tested negative for antibodies had been asymptomatic raising doubts about whether there could have been false test results or an undetectable immune response.
Background and Aims Renal amyloidosis include amyloid A (AA) and light chain (AL) as well as amyloidogenic leukocyte chemotactic factor 2 (ALECT2) and numerous hereditary forms. After identifying amyloidosis by its suggestive pale pink amorphous appearance in optic microscopy (OM) and Congo red positivity, a correct diagnosis of the amyloidogenic precursor protein is determinant to establish prognosis and treatment. Immunohistochemistry (IHC) and immunofluorescence (IF) studies use a limited number of antibodies to detect specific epitopes and may be difficult to interpret. The gold standard has become proteomics but laser microdissection and mass spectroscopy are not routinely available. Other options include electron microscopy with immunogold staining and complementary exams such as scintigraphy with 99mTc-DPD to detect transthyretin-related amyloidosis. Since the cause of amyloidosis vary among regions, analyzing local patterns can help establish a diagnostic procedure. We aimed at describing cases of kidney amyloidosis identified by biopsy during a 4-year interval and discuss possible implication for future diagnosis. Method We analyzed our kidney biopsy database and selected all cases of renal amyloidosis collecting clinical, laboratory and imaging data. Results From January 2016 until December 2019, 194 kidney biopsies were performed at the Hospital of Braga in the Portuguese province of Minho. Among these, 8 (4.1%) revealed amyloidosis. Mean age was 63.8±9.2 years of age, 5 were female, 6 were referred for nephrotic syndrome and 2 for what seemed like acute kidney injury. Mean creatinine at presentation was 3.2±2.3mg/dL. Among them, 2 had AL amyloidosis with light chain restriction by IF, 1 had AA amyloidosis with intense IHC stain and 5 patients had non-AL and non-AA forms of amyloidosis. Of these, 3 had probable fibrinogen A alpha-chain (AFib) amyloidosis, after a heterozygous mutation FGA p.Glu545Val was detected, 1, who did not have IHC performed, was assumed as having AA amyloidosis due to a history of serious recurrent infections and 1 is still under study. Four performed scintigraphy with 99mTc-DPD which was negative. The 2 patients with AL amyloidosis had, by OM, in one case glomerular and tubulointerstitial and on the other, glomerular and vascular involvement and, by IF, both had k light chain restriction. Both had additional cardiac and neurovegetative involvement, were treated with cyclophosphamide-bortezomib-dexamethasone and oral doxycycline with complete hematologic response and stabilization of kidney function. In 1 case, proteinuria only showed a slow decline 2 years after treatment. The 2 patients with AA amyloidosis had glomerular, vascular and tubular deposits. One had bronchiectasis and allergic bronchopulmonary aspergillosis and the other had common variable immunodeficiency with recurrent gastrointestinal and urinary infections with frequent bacteremia. None of them had confirmed extra-renal involvement, although the latter had hepatic fibrosis awaiting biopsy. Both progressed to dialysis soon after diagnosis. The 3 patients with AFib amyloidosis all had glomerular amyloidosis with additional amyloid deposition at tubular, vascular and both respectively. Two had had an increased creatinine and subnephrotic proteinuria for some years whereas 1 had kidney function decline and nephrotic syndrome in the course of few months. All were hypertensive and none had evident extra-renal deposits. Conclusion Identifying the amyloidogenic precursor may be difficult. Algorithms for diagnosis may vary according to local prevalence of specific types and available resources. AFib amyloidosis was very significant in our series. It was also described in 4.5% of hemodialysis patients in the district of Braga making it one of the first causes of amyloidosis in our region. This high prevalence may justify early genetic testing for the specific mutation in non-AL and non-AA forms.
Background and Aims Cardiovascular disease (CVD) is the major cause of mortality and morbidity in chronic kidney disease (CKD), especially in end-stage renal disease (ESRD) patients. Left ventricular hypertrophy (LVH) is a common cardiovascular complication in CKD. Growth differentiation factor (GDF)-15 increases in tissue injury and inflammatory states associated with cardiometabolic risk. GDF-15 and N-terminal pro B-type natriuretic peptide (NT-proBNP) are both synthesized by cardiomyocytes and may be associated with cardiorenal dysfunction. Our aim was to study the association of GDF-15 with LVH in ESRD patients on dialysis. Method This study included 196 ESRD patients on dialysis (hemodiafiltration and high-flux hemodialysis). Left ventricular mass (LVM) was evaluated through echocardiographic studies, corrected for body surface area and the values are presented as LVM index (LVMI). LVH was defined by a value of LVMI > 115 g/m2 in men and > 95 g/m2 in women. Patients were divided into two groups - LVH (n=131) and non-LVH (n=65). LVMI, clinical and analytical variables (age, body mass index, dialysis vintage, dialysis adequacy, GDF-15, NT-proBNP and pentraxin (PTX) 3 were evaluated. Results ESRD patients with LVH presented significantly higher levels of NT-proBNP and GDF-15, and a trend towards higher PTX3 values. In LVH patients, GDF-15 correlated positively and significantly with NT-proBNP and PTX3; LVMI correlated positively and significantly with pro-BNP and PTX3 levels; pro-BNP correlated significantly and positively with PTX3. Conclusion Our data show that in ESRD patients on dialysis with LVH, GDF-15 is raised and shows a strong association with NT-proBNP, PTX3 and LVMI. Further studies are needed to clarify if the rise in GDF-15 is a cause or a consequence of LVH development. Acknowledgments This work was supported by Applied Molecular Biosciences Unit-UCIBIO, financed by national funds from FCT/MCTES (UIDB/04378/2020), by North Portugal Regional Coordination and Development Commission (CCDR-N)/NORTE2020/Portugal 2020 (Norte-01-0145-FEDER-000024) and by REQUIMTE-Rede de Química e Tecnologia-Associação in the form of a researcher (S. Rocha) – project Dial4Life co-financed by FCT/MCTES (PTDC/MEC-CAR/31322/2017) and FEDER/COMPETE 2020 (POCI-01-0145-FEDER-031322).
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