Portuguese Journal of Nephrology & Hypertension

A Nephro-Obstetric outpatient clinic model

Chronic kidney disease (CKD) is increasing worldwide and studies estimate that around 6% of women of childbearing age suffer from kidney disease. Preconception counselling of women with CKD and their management during pregnancy requires a multidisciplinary team, with both nephrologists and obstetricians experienced in advising and taking care of women across the CKD spectrum, including dialysis patients and women with a kidney transplant. Here, the authors describe a model of a Nephro-Obstetric outpatient clinic, created in 2011, detailing their current clinical experience in the management of this complex population of women.

New Nephrology Departments: Challenges of the Future

Portugal has the highest incident of chronic kidney disease (CKD) in Europe and the incidence and prevalence of advanced CKD requiring renal replacement therapy are higher than in other occidental European countries. The development of new nephrology departments, even if these have no dialysis facilities, is crucial to curb the growth of this pathology which is already considered a public health problem. Despite the lack of resources, young nephrologists, who are a reflection of our excellent postgraduate education, are perfectly capable of planning, creating and leading these important new departments.

Predictors of peritonitis in peritoneal dialysis: experience during 3 decades

Introduction: Peritonitis is a common complication in peritoneal dialysis patients and a major cause for dropout. Systematic report and frequent trend analysis are thought to be major drivers for improvement in this area. The authors analysed peritonitis outcomes dating back over 20 years in a peritoneal dialysis unit of a central hospital. Methods: Retrospective study from 1993 to 2018: assessment of demographic, clinical and microbiological profiles of patients with peritonitis. We performed univariate and multivariate analysis (multiple logistic regression) to predict peritonitis risk factors, and survival analysis (Cox proportional hazards model) to determine the impact on outcomes (mortality and technique survival). Results: We included 225 patients, average age of 48.3±14.7 years, average time of follow-up of 38±25 months, with a total of 221 episodes of peritonitis (0.31 peritonitis/patient.year), 76% resulting in cure. Most frequent agents were Staphylococci: Coagulase-Negative (23%) and Staphylococcus aureus (19%, of which 24% were methicillin-resistant). Gram-negative infections led to higher rate of catheter removal, transfer to hemodialysis or death (49% of cases vs. 17% in Gram-positive). Primary end-point was death or transfer to hemodialysis, with a median time of 94 (min 4, max 94) and 66 (min 3, max 105) months, respectively. The occurrence of at least one peritonitis was the major variable that influenced transfer to hemodialysis (OR 3.94 [2.12 - 7.58], p < 0.001*], whereas an event in the first year also negatively affected the time to dialysis technique switch (median time 38.7 [26.2 - 58.4] vs. 67.8 [59.5 - 80.3] months, log-rank = 0.02*), but without impact on mortality. Only the peritoneal dialysis modality (OR: automated peritoneal dialysis vs. continuous ambulatory peritoneal dialysis 0.38 [0.19-0.74]) was predictive of peritonitis in multivariate analysis. Conclusions: In this single-center long-term analysis, where the rate of peritonitis was within recommended values, automated peritoneal dialysis seemed to have a protective impact. The number of peritonitis and peritonitis occurrence during the first year worsened technique survival, emphasizing early peritonitis prevention.

Therapeutic plasma exchange in patients in a portuguese ICU

Purpose: The aim of this study is to characterize a Portuguese Intensive Care Unit experience in therapeutic plasma exchange in critically ill patients. Methods: We performed a retrospective analysis of the patients treated with therapeutic plasma exchange between 2000 and 2019. Data on patient characteristics, therapeutic plasma exchange prescription, adjuvant therapy used, adverse events and outcome under treatment were collected. Results: A total of 101 therapeutic plasma exchange procedures in 20 patients were studied. Mean number of therapeutic plasma exchange sessions per patient was 5.1±1.3. The most frequent indications to begin this treatment were myasthenia gravis (25.0%) and anti-neutrophil-cytoplasmic antibody-associated vasculitis (15.0%). There were 45.5% adverse events and the most frequent was hypotension (15.2%). 98% of the complications were mild-to-moderate. The outcome was favorable in 60.0% of patients. Conclusion: Therapeutic plasma exchange is an effective and safe therapy in many diseases that had high morbidity and mortality prior to the use of this technique.

ABO-incompatible living donor kidney transplantation in Portugal

Introduction: ABO incompatibility was considered a barrier to kidney transplant. However, the shortage of available organs for transplantation and the excellent long-term results further establish ABO-incompatible (ABOi) as a safe and effective therapeutic strategy. The aim of the present study was to evaluate the outcomes of ABOi transplantation in terms of graft survival and function, rejection episodes and infections complications. Methods: The authors present a single-center retrospective observational study in a unit with approximately 370 living donor kidney transplants registered. This study includes the analysis of 12 patients who underwent ABOi living donor kidney transplantation between November 2014 and July 2019. Desensitization protocol consisted of intravenous Rituximab 375mg/m2 single dose administration 2 weeks pretransplant. Tacrolimus and Mycophenolate Mofetil were started before transplantation one week and 48 hours respectively. Plasmapheresis was performed to remove anti-A or B antibodies until their titers were <1:8 during the first post-operative week and <1:16 at the second. All kidney recipients of both ABOi grafts received Basiliximab (20mg on days 0 and 4) as antibody induction therapy. Maintenance immunosuppression consisted of Tacrolimus, Mycophenolate Mofetil and corticosteroid. Results: A total of 12 patients were included in the study, 75% male; 43 years (IQR 31-50). The most common blood group mismatch was A to O (n=4; 33%). In the first year, 2 of patients (25%) developed acute rejection. The follow-up time was 17 months (IQR 7-36). Five patients (42%) developed infectious complications. None patients developed cytomegalovirus or BK polyomavirus infections. At the end graft and patient survival were 100%. Conclusion: ABOi kidney transplantation has become a routine procedure. With this approach, about 30% of living donors who were refused in the past can now donate their kidneys and thereby significantly expand the living donor pool. The immunosuppressive protocol of this unit can be considered safe.

Hyperuricemia in Chronic Kidney Disease: a role yet to be explained

The role of uric acid as an independent risk factor for chronic kidney disease development and progression is still a matter of discussion. Several observational studies showed a positive association between hyperuricemia and the progression of kidney dysfunction, but others did not, which probably derived from different biases and studies insufficiencies. Moreover, the results from studies on patients in hemodialysis and peritoneal dialysis are even more controversial, with some evidence pointing towards a protective role of uric acid in hemodialysis patients, but not in peritoneal dialysis. In addition to most evidence suggesting a role of uric acid in chronic kidney disease pathogenesis and progression, pharmacological treatment of asymptomatic hyperuricemia is still not indicated, with no consensus on either the uric acid level at which treatment would be beneficial, or the target-level to achieve. There are several studies on the renal benefits of xanthine oxidase inhibitors allopurinol and febuxostat, with heterogeneous results. Most of them showed a renoprotective effect of both drugs, delaying renal disease progression. However, the different results found in other studies makes it difficult to draw definitive conclusions. Despite recent evidence pointing toward an important role of uric acid in the pathogenesis and progression of kidney disorders, and the benefits of its treatment, there are still several unanswered questions, and well-conducted studies are needed to make valid conclusions.

Doppler Ultrasound in Vascular Access care: the pearls and pitfalls of flow volume measurement

Vascular access (VA) care is a critical part of the management of end-stage renal disease. Optimal care is necessary to avoid underdialysis and VA loss, leading to increased morbidity, mortality, and health-care-associated costs. The cornerstone of VA surveillance is flow volume (Qa) measurement. One of the most common ways to quantify Qa in clinical practice is by using duplex ultrasound (DUS), which is based on the Doppler method. DUS is a cheap and non-invasive technology that allows direct Qa measurement and the simultaneous visualization of the VA morphology, which allows the diagnosis of underlying lesions. In addition, DUS has a similar precision to Ultrasound Dilution (UD) methods. On the other hand, DUS is an operator-dependent technique, has more potential measurement errors, is time-consuming, and also loses accuracy in higher Qa. This narrative review aims to discuss the theory and technical considerations behind DUS, as well as its advantages, disadvantages, and pitfalls. We also review the reliability of DUS measurement and its correlation with UD methods. Finally, we reflect on the role of DUS Qa measurements in arteriovenous fistula maturation and surveillance. Despite the overall quality of data regarding VA surveillance not being high, we believe that DUS will remain one of the most important tools at our disposal in every step of VA care.

Treatment of lupus nephritis - past, present and (near) future

The management of lupus nephritis is challenging for most nephrologists. Many trials have brought only a certain degree of evidence to the diagnosis and treatment of this disease, and many questions remain unanswered. In this review, we will explore the path traveled so far and the steps that are likely to happen in the near future.

Can cryoglobulinemia trigger ANCA vasculitis?

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a rare and heterogeneous group of autoimmune diseases. These pauciimmune vasculitis differ from the cryoglobulinemic vasculitis mediated by immune complexes. We report the case of a 79-year-old male with silicosis and chronic alcoholic liver disease, presenting with a rapidly progressive glomerulonephritis and pancytopenia. Work-up revealed hypocomplementemia, polyclonal hypergammaglobulinemia, type 3 cryoglobulinemia, p-ANCA positivity and elevated anti-MPO. Renal biopsy showed a pattern of chronic interstitial nephritis with fibrocellular crescents, and immunofluorescence staining was negative. Treatment was started with corticosteroids and rituximab with improvement of the renal function, decrease of the anti-MPO titer and disappearance of the cryoglobulinemia. In this case, renal injury was caused by ANCA vasculitis, whose etiology remains unknown despite the recognizable risk factor for ANCA formation (silicosis). The importance of the cryoglobulinemia is not clear, as it could be part of the pathogenesis or just an epiphenomenon secondary to the autoimmune and the chronic liver diseases.

Primary hyperoxaluria type 1 - two case reports

Background: Primary hyperoxaluria type 1 is a rare autosomal recessive inherited disease, caused by mutations in AGXT gene, with an estimated incidence of 1:100.000 live births per year in Europe. Over 50% present with end stage renal disease at diagnosis. Case reports: The first case is a 14-year-old boy, second child to consanguineous parents, with history of recurrent lithiasis and ureteral dilatation starting 5 years before. Urine/stone analysis revealed calcium oxalate monohydrate crystals and markedly elevated urine oxalate excretion. Genetic tests confirmed a mutation in AGXT gene, c.1151T>C, in homozygosity. Two years after, nephrocalcinosis was identified and glomerular filtration rate gradually declined. Oxalate deposition in solid organs was excluded and successful orthotopic liver transplantation was performed, with stabilization of glomerular filtration rate. The second case is a 16-year-old girl, with recurrent episodes of renal colic. At diagnosis, she had obstructive hydronephrosis, multiple kidney stones and an estimated glomerular filtration of 42.1mL/min/1.73m2. Metabolic study showed hypocitraturia and hyperoxaluria. With dietetic measures and irregular treatment, urine oxalate excretion remained high but renal function improved. Genetic tests confirmed the presence of two pathologic variants in AGXT gene: c.731T>C and c.1151T>C in compound heterozygous. Conclusions: Recurrent urolithiasis and nephrocalcinosis in children along with family history/consanguinity should raise the suspicion of Primary Hyperoxaluria type 1. Conservative treatment may increase renal survival. Effects of systemic oxalosis must be screened when glomerular filtration rate declines below 30-50mL/min/1.73m2, and sequential or combined liver and kidney transplantation should be considered.

Sarcoidosis: a case with pulmonary, cutaneous and renal injury

Sarcoidosis is a rare multisystem disease that is characterized by the formation of inflammatory granulomatous processes. The lung is the most frequently affected organ, but kidney injury can also occur. It is a disease with a highly variable course and prognosis and non-consensual treatment. This report describes the successful case of a patient with sarcoidosis presenting with pulmonary, cutaneous and renal injury, who presented with adequate diagnostic timing and optimal therapy response.

A physiological approach to recurrent nephrolithiasis and its genetic determinants

We report a case of a 63-year-old patient with recurrent nephrolithiasis for over 40 years and a significant family history of nephrolithiasis. The patient underwent full investigation at our department. He presented hypercalcemia, hypophosphatemia and hypercalciuria, with parathyroid hormone level in the normal range. A calcium load test and a fluorocholine PET-CT excluded primary hyperparathyroidism. Abnormal secretion of parathyroid hormone-related protein and sarcoidosis were also excluded. Genetic analysis showed mutations encoding for 25(OH)-vitamin D3-24-hydroxylase (CYP24A1) and Na-dependent phosphate cotransporter 2c (SLC34A3). This case affords insights into the biological pathways that underlie the role of genetic inheritance and accrued risk of development of nephrolithiasis.

Anemia, thrombocytopenia and acute kidney injury - a diagnostic challenge

Acute Kidney Injury in patients referred for ECMO therapy