Portuguese Journal of Nephrology & Hypertension

Kidney fibrosis in disease and aging - The stage and some key actors

Make Urine Great Again

Some reflections on renal care

Henoch-Schönlein Purpura: What to expect

Introduction: Henoch-Schönlein Purpura is the most common systemic small vessel vasculitis of childhood. It is most frequently a selflimited entity, although some cases with concomitant nephritis may have serious complications. This study aims to analyze the clinical, epidemiologic and prognostic factors of children with this disease. Methods: Observational and retrospective study of children with diagnosis of Henoch-Schönlein Purpura from January 2011 to June 2017. Results: 61 patients were identified, with a median age of 6 years and a slight predominance of females. Purpura was present in all cases; the second most common symptom was arthralgia (75.4%), followed by gastrointestinal (39.3%), renal (31.1%) and scrotal involvement (6.6%). Corticotherapy was used in 12 patients (19.7%). Almost one fourth of the patients had a recurrence, but only 4 had persistent manifestations for longer than 6 months. Abdominal symptoms were found to have a positive correlation with renal involvement and corticotherapy showed no protective long-term effects. Discussion: Henoch-Schönlein Purpura is mostly a self-limited pathology. We found no association between age or sex and a poorer outcome, but a correlation between abdominal and renal involvement was found. We found a negative correlation between joint involvement and recurring episodes, showing that it may be a good prognostics factor. Corticotherapy demonstrated no protective long-term effect, and was on the contrary correlated with hospitalization, recurrence and persistence of signs and/or symptoms. This correlation can be explained by the fact that patients having indication for and receiving corticotherapy had an inherently more severe spectrum of the disease and so were more prone to poorer outcomes.

The Charlson Comorbidity Index - its impact on hospitalization and mortality in chronic renal disease

Introduction: Renal replacement therapy has not always been shown to benefit end-stage renal failure patients who are elderly or have multiple comorbidities. The Charlson Comorbidity Index (CCI) predicts mortality and is frequently used for risk stratification in clinical practice. We evaluated correlation between the Charlson Comorbidity Index and hospital admissions and mortality in chronic kidney disease patients. Methods: This retrospective observational study included 693 patients with an estimated glomerular filtration rate (eGFR)<30 ml/min/1.73m2, followed in pre-dialysis medical appointments (2008-2012). Based on the CCI, the subjects were collapsed into 4 risk groups: <25th percentile (CCI≤5.2; n=172) - G1; 25-50th percentile (CCI: 5.3-6.4; n=162) - G2; 50-75th percentile (CCI: 6.5-7.4; n=177) - G3; and >75th percentile (CCI≥7.5; n=182) - G4. Descriptive statistics, ANOVA, the chi-square and the log-rank tests were used for comparison between groups. The Bonferroni test was used as a post-hoc test. Kaplan-Meier analysis was used to evaluate mortality. Results: Mean age was 70.1 years, 54% women, with an eGFR of 20.2±9.2 ml/min (Modification of Diet in Renal Disease). G1 patients were younger (p<0.001) and showed higher hemoglobin (p<0.001), eGFR (p=0.025), calcium (p=0.033) and albumin (p<0.001). In a multivariate logistic regression model adjusted for gender, age, hemoglobin, phosphorus, parathormone, eGFR, albumin and blood pressure, CCI is a risk factor for hospitalization (ORa=1.362, Cl 95% 1.175-1.580, p<0.0001). Multivariate Cox regression analysis identified higher scores of CCI as an independent risk factor for cardiovascular mortality (HRa=1.24, Cl 95% 1.053-1.467, p=0.010). Survival at 85 months was progressively shorter with higher CCI (G1=86.7%, G2=65.9%, G3=59.35 % and G4=30.4%, log-rank=34.465, p=0.0001). Conclusion: The Charlson Comorbidity Index was shown to be a strong predictor of mortality and hospitalizations in patients with stage IV chronic kidney disease. It might be a valuable tool in dialysis decision-making for patients with advanced chronic kidney disease and severe comorbidity burden.

Hypothyroidism and chronic kidney disease: An undervalued two-way relationship

There is long-standing evidence that thyroid disease and kidney disease have a two-way relationship, as they can aggravate and lead to each other. The exact nature of this association and its clinical implications have been a matter of debate, as co-sharing of risk factors and appropriate prospective studies that allow for causal relationships to be inferred are lacking. Hypothyroidism is currently regarded by the American Heart Association as a modifiable cardiovascular risk factor and a reversible cause of heart failure. Among the nephrology community, while hypothyroidism has been an increasingly prevalent issue, formal guidelines on how to proceed when such association occurs are lacking and its clinical implications are often underappreciated among practitioners. Whether renal disease caused the thyroid disturbance or vice-versa, there is evidence pointing to thyroid dysfunction being a risk factor for incident chronic kidney disease and its progression and it is linked to increased overall mortality in CKD patients. The authors provide a review of current scientific evidence on this complex relationship.

Nephrotoxicity in patients receiving immune checkpoint inhibitors

Over the last years, immunotherapy has become part of the most important strategies to treat some types of cancer. Immune checkpoint inhibitors are within this new class of drugs and consist of monoclonal antibodies that target inhibitory receptors expressed on T cells. While revolutionary results have been achieved with these therapies, their widespread use has also brought to light multiple immune-related adverse effects that impact the patients quality of life and survival, posing new challenges to clinicians. The kidney is one of the affected organs, and nephrotoxicity has probably been underestimated in the first clinical trials. The etiopathogenic mechanisms involved and the management of renal disease in this context are not fully known. This review aims to illustrate the most recent data on the clinical presentation, diagnosis, treatment, and behavior of patients with kidney complications of immune checkpoint inhibitors, including particularly vulnerable subjects, such as transplant recipients. A growing number of patients are being handled with these drugs, and nephrologists are expected to be part of the multidisciplinary approach required by the new immunotherapies

Magnesium supplementation to prevent recurrence of renal stones

Stone formers have lower urinary magnesium than healthy people. Higher urinary magnesium levels are associated with lower incidence of kidney stones, and hypomagnesuria has been described as a lithogenic risk factor. Magnesium can have direct and indirect inhibitory effects on lithogenesis: decreasing the absorption of oxalates in the intestine; forming magnesium oxalate complexes which reduces the saturation of calcium oxalate; increasing the urinary citrate and inhibiting the conversion of the calcium oxalate in its monohydrated form. Oral supplementation with magnesium is an effective way to correct hypomagnesuria. However, oral magnesium supplementation in recurrent stone formers with hypomagnesuria is still a subject of ongoing debate, and physicians treating these patients underestimate its potential preventive effects. Oral magnesium supplementation can be used as an adjuvant therapy to the standard prophylactic therapy, mainly in association with an alkali salt. It is well tolerated and has few adverse effects.

Alternative pathway complement activation in secondary thrombotic microangiopathies: is genetics the smoking gun?

IgA Nephropathy with Thrombotic microangiopathy: Is this secondary thrombotic microangiopathy or IgA nephropathy-triggered atypical Hemolytic Uremic Syndrome?

IgA Nephropathy (IgAN) is the most prevalent biopsy-proven primary glomerular disease worldwide. Historically, thrombotic microangiopathy (TMA) was associated with IgAN in cases of severe hypertension or advanced chronic kidney disease, but recent data suggest that complement activation plays a crucial role in the development of TMA in IgAN. We report a case of Crescentic IgAN with complement-mediated TMA (C-TMA) in a 27-year old male patient with a pathological missense mutation in heterozygosity in the CFH gene and a rare variant in the C3 gene, treated with steroids, cyclophosphamide and plasmapheresis without recovery of kidney function. We also discuss other treatment possibilities and kidney transplant options. Additionally, we will review the latest advances that are enhancing our understanding of the association between IgAN and TMA

Cryoglobulinemic HCV-related membranoproliferative glomerulonephritis with TMA - secondary HUS or infection-triggered aHUS?

Introduction: Membranoproliferative glomerulonephritis is a pattern of glomerular injury on renal biopsy with characteristic light microscopic changes, namely mesangial hypercellularity, endocapillary proliferation and double contour formation along the glomerular capillary walls. This pattern does not represent a disease per se but can occur as a result of different pathologic processes. Case Presentation: We present a case of a 37-year-old caucasian female patient with thrombotic microangiopathy (TMA), severe hypertension and immune-complex-mediated glomerulonephritis, secondary to hepatitis C virus (HCV) infection. Steroid therapy and fresh-frozen plasma infusions were started, with progressive improvement of lab results. Treatment of HCV infection was started with direct-acting antiviral therapy. The results of the genetic study of the complement alternative pathway regulatory proteins were positive for a homozygote variant of the gene CFHR5 (p.Val110Ala) and a homozygote deletion on CFHR3/CFHR1 proteins. Discussion: Hypertension is commonly associated with TMA and could explain the features of this case. Nevertheless, the differential diagnosis is often difficult because TMA caused by hypertension is indistinguishable from all other entities. The finding of a homozygote variant of the gene CFHR5, and a homozygote deletion on CFHR3/CFHR1 proteins, raised the possibility that this case might have been an Atypical Hemolytic Uremic Syndrome (aHUS) triggered by the endothelial damage caused by the HCV-related cryoglobulinemic glomerulonephritis

Gemcitabine-associated thrombotic microangiopathy - a role for eculizumab?

Gemcitabine-associated thrombotic microangiopathy (gTMA) is a rare entity that is usually associated with a poor prognosis, with loss of kidney function and often death. The management of this syndrome includes discontinuation of the drug. Other approaches have been tried, with no proven efficacy and inconsistent results, such as glucocorticoids, intravenous immunoglobulin, plasma infusion and rituximab. Drug-induced hemolytic uremic syndrome, a form of thrombotic microangiopathy (TMA), has shown good response to the anti-C5 monoclonal antibody eculizumab and anecdotal cases have been reported where eculizumab improved gTMA. We present a case where a patient with gTMA on hemodialysis was treated with eculizumab, with full recovery of hematological disorders and kidney function. We suggest that clinicians be aware of gTMA as a potentially life-threatening condition and that eculizumab should be considered as a possible first-line agent.

Nephrotic syndrome in a patient with metastatic melanoma: beyond the obvious

Nephrotic syndrome in a patient with metastatic melanoma can occur in the context of a paraneoplastic glomerulopathy or as a complication of treatment. New oncologic immunotherapies, including immune checkpoint inhibitors, have been frequently associated with interstitial nephritis and, in rare cases, with nephrotic syndrome. This article presents the case of a 52-year-old man diagnosed with metastatic melanoma who was admitted with acute kidney injury and nephrotic syndrome after having started immune checkpoint inhibitors. After investigation, acute kidney injury was attributed to immunotherapy-associated acute interstitial nephritis, and nephrotic syndrome was found to be the result of AA amyloidosis, which is a rare complication of metastatic melanoma.