Lessons from Four Decades of Systemic Amyloidosis with Renal Involvement.

BACKGROUND: Apart from ATTR amyloidosis, the epidemiology and outcomes of the most common subtypes of systemic amyloidosis in Portugal remain primarily unknown. METHODS: This retrospective cohort study evaluated patients with renal biopsy-proven amyloidosis, diagnosed from January 1978 to December 2019. Follow-up started at kidney disease presentation and ended at death or August 2020. Clinical presentation, survival, and prognostic factors were analysed. RESULTS: Of 123 patients with amyloid nephropathy, 111 had definite amyloid typing and were analysed. AA amyloidosis was the most frequent type (56.1%) and was related mainly to chronic infection (47.8%) and chronic inflammatory arthritis (29.0%). AL amyloidosis was present in 25.2% of patients and hereditary forms in 6.5% (4.1% AFibE526V, 2.4% ATTRV30M). During follow-up, 73.9% of AA and 54.8% of AL patients progressed to end-stage renal disease, and 79.7% of AA and 77.4% of AL died; median overall survival was 66.0 (95% CI, 33.0-99.0) and 18.0 (95% CI, 9.3-26.7) months (p = 0.025), respectively. There were no significant differences in renal outcome and survival on dialysis between these two types. In multivariate analysis, cardiac involvement at presentation (HR 6.26 [95% CI, 2.89-13.56]) and estimated glomerular filtration rate <30 mL/min/1.73 m2 (HR 2.05 [95% CI, 1.06-3.99]) independently influenced AA and AL amyloidosis survival. Cardiac involvement at presentation was an independent predictor of death (HR 9.65 [95% CI, 2.91-31.95]) and early mortality in AL amyloidosis. CONCLUSIONS: In Portugal, AA amyloidosis and related chronic infections are still relevant. Regarding AL amyloidosis, the low incidence and advanced disease at presentation result from missed and erroneous diagnoses, leading to delayed referrals and poor outcomes in these patients.

C3 Glomerulonephritis Presenting With Nephritic and Nephrotic Syndromes: Spontaneous Remission After Six Months on Dialysis.

C3 glomerulopathy is a rare and complex renal disease driven by complement dysregulation, with variable presentation and pathophysiology. We report the case of a middle-aged male patient presenting with nephritic and nephrotic syndromes and low serum C3, whose biopsy established the diagnosis of C3 glomerulonephritis. He was found to be homozygous for the complement factor H-related protein (CFHR)3-CFHR1 deletion, which has been associated with the development of anti-factor H autoantibodies. However, the lack of consistent and accessible nephritic factor assays prevented full clarification of the mechanisms involved in the disease. Interestingly, despite not receiving treatment due to suspicion of malignancy and perceived poor renal prognosis, there was spontaneous recovery after six months on hemodialysis. This case reflects the enduring challenges in establishing the diagnosis and prognosis of C3 glomerulonephritis.

Circulating Renalase as Predictor of Renal and Cardiovascular Outcomes in Pre-Dialysis CKD Patients: A 5-Year Prospective Cohort Study.

Chronic kidney disease (CKD) is an independent risk factor for adverse cardiovascular and cerebrovascular events (MACCEs), and mortality since the earlier stages. Therefore, it is critical to identify the link between CKD and cardiovascular risk (CVR) through early and reliable biomarkers. Acknowledging that CKD and CKD progression are associated with increased sympathetic tone, which is implicated in CVR, and that renalase metabolizes catecholamines, we aimed to evaluate the relationship between renalase serum levels (RNLS) and cardiovascular and renal outcomes. The study included 40 pre-dialysis CKD patients (19F:21M) with median age of 61 (IQ 45-66) years. At baseline, we measured RNLS as well as routine biomarkers of renal and cardiovascular risk. A prospective analysis was performed to determine whether RNLS are associated with CKD progression, MACCEs, hospitalizations and all-cause mortality. At baseline, the median level of RNLS and median estimated glomerular filtration rate (eGFR) were 63.5 (IQ 48.4-82.7) µg/mL and 47 (IQ 13-119) mL/min/1.73 m2, respectively. In univariate analysis, RNLS were strongly associated with eGFR, age and Charlson Index. Over the course of a mean follow-up of 65 (47 to 70) months, 3 (7.5%) deaths, 2 (5%) fatal MACCEs, 17 (42.5%) hospital admissions occurred, and 16 (40%) patients experienced CKD progression. In univariate analysis, RNLS were associated with CKD progression (p = 0.001), hospitalizations (p = 0.001) and all-cause mortality (p = 0.022) but not with MACCEs (p = 0.094). In adjusted analysis, RNLS predicted CKD progression and hospitalizations regardless of age, Charlson comorbidity index, cardiovascular disease, hypertension, diabetes and dyslipidemia. Our results suggest that RNLS, closely related with renal function, might have a potential role as predictor of renal outcomes, hospitalizations, and mortality in pre-dialysis CKD patients.

Severe L-asparaginase-induced Hypertriglyceridaemia Treated with Plasmapheresis.

L-asparaginase is used for the treatment of acute lymphoblastic leukaemia. Hypertriglyceridaemia is a side effect and associated with potentially fatal complications, including acute pancreatitis. Plasmapheresis may have a role in treatment when triglycerides are >2000 mg/dl. We report the case of a 39-year-old woman treated with L-asparaginase for acute lymphoblastic leukaemia, who developed severe hypertriglyceridaemia (6560 mg/dl) and acute pancreatitis. Intravenous insulin infusion was started, along with fenofibrate and atorvastatin administration, and platelet transfusion. Plasmapheresis was carried out leading to a frank decline in serum triglyceride levels (366 mg/dl), a decrease in pancreatic enzymes and clinical improvement. The diagnosis of pancreatitis secondary to L-asparaginase should lead to immediate drug withdrawal, and plasmapheresis should be considered when serum triglyceride values exceed 2000 mg/dl. In our case, there was a 95% triglyceride removal rate. This response illustrates the strong effectiveness of early treatment with plasmapheresis in severe and symptomatic hypertriglyceridaemia associated with L-asparaginase. LEARNING POINTS: Pancreatitis following L-asparaginase-induced hypertriglyceridaemia is a severe and potentially reversible condition in both adults and children treated for acute lymphoblastic leukaemia.Early plasmapheresis is more effective to rapidly decrease serum triglycerides.

Endothelial Dysfunction Is Associated with Cerebrovascular Events in Pre-Dialysis CKD Patients: A Prospective Study.

BACKGROUND: Patients with chronic kidney disease (CKD) have markedly increased rates of end stage renal disease, major adverse cardiovascular/cerebrovascular events (MACCEs), and mortality. Endothelial dysfunction (ED) is an early marker of atherosclerosis that is emerging as an increasingly important non-traditional cardiovascular risk factor in CKD. There is a lack of clinical studies examining the association between ED and both cardiovascular and renal endpoints in patients with CKD. AIMS: We examined the association between reactive hyperemia index (RHI), a validated measure of endothelial function measured by peripheral arterial tonometry (PAT), with traditional cardiovascular risk factors in pre-dialysis CKD patients and prospectively evaluated the role of RHI as predictor of renal and cardiovascular outcomes in this population. METHODS: One hundred and twenty pre-dialysis patients with CKD stages 1 to 5 (CKD group) and 18 healthy kidney donor candidates (control group) were recruited and had a successful RHI measurement by PAT. General demographic and clinical information including traditional cardiovascular risk factors were registered from all participants. Thereafter, patients were prospectively followed-up for a median time of 47 (IQR 19-66) months to determine associations of RHI with renal outcomes, MACCEs, hospitalizations or mortality. RESULTS: In the CKD patient population, the mean age was 57.7 ± 15.5 years, the mean eGFR was 54.9 ± 36.7 mL/min/1.73 m2 (CKD-EPI) and 57 were males (47.5%). At baseline, in univariate analysis, RHI in the CKD group correlated positively with eGFR (r = 0.332, p < 0.0001) and correlated negatively with age (r = -0.469, p < 0.0001), Charlson index (r = -0.399, p < 0.0001), systolic blood pressure (r = -0.256, p = 0.005), and proteinuria (r = 0.211, p = 0.027). Reactive hyperemia index in the control group did not significantly differ from RHI observed in patients with CKD stages 1 to 5 (2.09 ± 0.40 vs. 2.01 ± 0.06, p = 0.493). In adjusted analysis, only age (ß = -0.014, p = 0.003) remained independently associated with RHI at baseline. During follow-up, 8 patients suffered a MACCEs, 33 patients experienced renal function deterioration, 17 patients were hospitalized for medical reasons and 6 patients died. RHI at baseline was not significantly associated with CKD progression (1.94 vs. 2.02, p = 0.584), hospitalizations (1.90 vs. 2.04, p = 0.334), and all-cause mortality (1.65 vs. 2.01, p = 0.208) or MACCEs (1.77 vs. 2.01, p = 0.356), but was significantly associated with cerebrovascular events (1.27 vs. 2.02, p = 0.004) and with a composite cardiovascular outcome (MACCEs, hospital admissions and death; 1.73 vs. 2.07, p = 0.035). Conclusion: Our results suggest that RHI may be a predictor for the development of cerebrovascular events in pre-dialysis CKD patients who may benefit from more aggressive preventive measures.

Clearing the clouds: Case-report and review of the literature.

In peritoneal dialysis (PD), a cloudy dialysate is an alarming finding. Bacterial peritonitis is the most common cause, however, atypical infections and non-infectious causes must be considered. A 46-year-old man presented with asthenia, paraesthesia, foamy urine and hypertension. Laboratory testing revealed severe azotaemia, anaemia, hyperkalaemia and nephrotic-range proteinuria. Haemodialysis was started through a central venous catheter. Later, due to patient preference, a Tenckhoff catheter was inserted. Conversion to PD occurred 3 weeks later, during hospitalization for a presumed central line infection. A month later, the patient was hospitalized for neutropenic fever. He was diagnosed an acute parvovirus infection and was discharged under isoniazid for latent tuberculosis. Four months later, the patient presented with fever and a cloudy effluent. Peritoneal fluid (PF) cytology was suggestive of infectious peritonitis, but the symptoms persisted despite antibiotic therapy. Bacterial and mycological cultures were negative. No neoplastic cells were detected. Mycobacterium tuberculosis eventually grew in PF cultures, despite previous negative molecular tests. Directed therapy was then initiated with excellent response. Thus, facing a cloudy effluent, one must consider multiple aetiologies. Diagnosis of peritoneal tuberculosis is hampered by the lack of highly sensitive and specific exams. Here, diagnosis was only possible due to positive mycobacterial cultures.

Visceral Dissemination of Mucocutaneous Leishmaniasis in a Kidney Transplant Recipient.

Intracellular protozoan of the genus Leishmania, endemic in the Mediterranean basin, are the cause of cutaneous (CL), mucocutaneous (MCL), and visceral leishmaniasis (VL). A 75-year-old woman was admitted nine years after a second kidney transplant (KT), due to persistent pancytopenia and fever. She presented edema and erythema of the nose in the last two years and an exophytic nodular lesion located on the left arm, with areas of peripheral necrosis and central ulceration in the last 18 months. A bone marrow biopsy revealed features compatible with Leishmania amastigotes, and polymerase chain reaction test (PCR) for Leishmania infantum was positive. Moreover, biopsy and PCR for L. infantum of the cutaneous lesion on the patient's left arm and nose and PCR from peripheral blood were positive. Thus, a diagnosis of CL, MCL, and VL was made, and liposomal amphotericin B was initiated, but the patient had an unfavorable outcome and died. This is the first report of a KT recipient presenting with the entire spectrum of leishmaniasis. In Portugal, this infection is rare-so a high degree of clinical suspicion is required for its diagnosis, especially in endemic regions, as visceral leishmaniasis is a potentially life-threatening infection.