Portuguese Journal of Nephrology & Hypertension

Portuguese consensus document statement in diagnostic and management of atypical hemolytic uremic syndrome

Among thrombotic microangiopathies (TMA), the hemolytic uremic syndrome associated with dysregulation of the alternative complement pathway (aHUS) is one of the most challenging diseases a nephrologist can face. By the end of the XXth century, the complements role was unraveled with the discovery that mutations in the factor H coding gene were responsible for aHUS. But it was the acknowledgment that pharmacological C5-9 blockage provided a cure for aHUS that fostered the interest of the nephrology community in the genetics, pathophysiology and therapeutics of, not only of aHUS, but TMA in general. The molecular genetics of aHUS is technically demanding and, as such, in Portugal (alike many other European countries) a single laboratory emerged as a national reference center. The fact that all samples are evaluated in a single center provides a unique opportunity for data collection and a forum for discussion for all those interested in the field: immunologists, molecular geneticists, pathologists and nephrologists. The current consensus document emerged from such a discussion forum and was sponsored by the Portuguese Society of Nephrology. The goal is more to portray the Portuguese picture regarding the diagnostic approach and therapeutic options than to extensively review the state of the art of the subject. The accompanying documents that are published as supplementary data are in line with that goal. They range from the informed consent and clinical form to be sent together with the biological samples for genetic testing, to the appendix regarding the actual sampling and storing conditions. The document is also intended to set an example for future documents and independent discussion forums on other kidney diseases for which emerging diagnostic and/or therapeutic strategies are reaching clinical practice

Transitions of care management in CKD: critical thinking and improving strategies

Chronic kidney disease (CKD) has a high clinical and socioeconomic impact and is often associated with multimorbidity. Improved treatment has allowed an increase in patient survival, but patient life expectancy remainslimited. The disease course has a continuum of lesion, stage and treatment transitions. The focus is often placed on treatment modality, disregarding the course of a CKD patients disease. In addition, patient management in transitions of modalities of renal replacement therapy (RRT) can also be a vector for improving clinical outcomes. The transition between different types of CKD treatment and the transition of care from paediatric to adult team are critical processes throughout the life of a CKD patient. In the therapeutic transition, there is the need to identify better predictors of success in allocating patients with stage 5 CKD to their first dialytic modality in. There is a risk of early mortality in the induction period of dialysis, particularly of the elderly in extracorporeal dialysis regimens. Doubt remains in decision making about the ideal timing to establish the transition to renal replacement therapy and its most appropriate type. Transfer between dialytic modalities also calls for opportune and integrated policies protecting vascular resources. Renal transplantation is considered the optimal renal replacement therapy; however, transplant failure or the side effects of immunosuppression are threats to consider, which may redirect these patients back to dialysis and involves a re-evaluation of the patients status. Also, end-of-life care and decision making between initiating renal replacement therapy or maintaining conservative management are a challenge in the elderly. This review identifies the main challenges in these transitional processes, raising awareness of areas in need of improvement in patient care. The aim should be to achieve a more comprehensive and appropriate health management than a limited focus on CKD modality treatment.

Interventional nephrology - five years dealing with central stenosis: immediate and long-term results

Introduction: Improved technique and materials have allowed us to prolong the life of hemodialysis vascular access using percutaneous transluminal balloon angioplasty (PTA). Central vein stenosis (CVS) can lead to arteriovenous access dysfunction or thrombosis. Our goal was to revise the outcomes of our institution, evaluating the immediate and long-term results in the endovascular treatment of CVS. Methods: We reviewed the data of all procedures performed in our center, Centro Hospitalar e Universitário de Coimbra, during a five-year period July 2009 and June 2014, selecting the cases that had a CVS diagnosis. We evaluated the immediate result and the existence of complications during the procedure. Long-term evaluation of PTA results of the 26 patients with a successful PTA was made through contact with the referring hospital or hemodialysis clinic. Primary and assisted access patencies were verified retrospectively at 3, 6, 12 and 24 months post-intervention. Results: Of the 31 patients in whom there were an intention to treat, in 5 the stenosis was in fact an occlusion and the guide wire could not be passed. The remaining 26 patients underwent PTA with improvement/resolution of the lesion. Consequently, we had an initial intervention success rate of 83.9%. Minor complications occurred in 2 patients. The long-term follow-up results were primary patency at 3, 6, 12 or 24 months of 88%, 63%, 31% and 6%, respectively, and assisted primary patency at 3, 6, 12 or 24 months of 88%, 76%, 70% and 46%, respectively. Conclusion: CVS is a common problem in hemodialysis patients. Our center results are consistent with current literature and demonstrate the benefit of PTA with excellent immediate success. However, the high recurrence rate of these stenoses requires in many cases multiple PTA, with low long-term primary patency.

Peritoneal dialysis catheter placement with percutaneous technique with fluoroscopic guidance - our center’s experience

Introduction: Studies have shown no clear superiority between surgical and percutaneous methods for peritoneal dialysis (PD) catheter insertion, so the preferred method usually depends on each centers experience. In our center we perform both percutaneous technique with fluoroscopic guidance (PTFG) and laparoscopic technique (LT). Objective: Our main goal is to present our experience with PTFG and our results. We also aim to compare PTFG with LT in terms of complications associated with catheter placement and 1-year catheter survival. Methods: We performed a retrospective study that included the 17 incident patients submitted to first PD catheter placement using PTFG from 28th October 2014 to 15th March 2018 and the last equivalent number of patients that were submitted to first PD catheter placement using LT, until 15th March 2018. Results: We observed no statistically significant differences between groups with respect to 1-year catheter survival and complications related to PD catheter insertion, apart from dialysate leakage, which was higher in the LT group. There were complications to take into account in the PTFG group. Conclusion: PTFG performed by nephrologists seems to be an effective technique for PD catheter placement, although no substitution for surgical techniques when clinically indicated, and results can be improved with increased experience with this technique.

Nephrolithiasis in a portuguese pediatric population

Introduction and Aims: Nephrolithiasis incidence in children has increased considerably. It is associated with substantial morbidity, recurrence and increased adulthood cardiovascular risk and chronic kidney disease. A thorough investigation is essential, as rare forms of urolithiasis have increased risk of renal failure. We aim to determine the epidemiology and outcomes of a pediatric population with nephrolithiasis presented in a nephrology unit of a tertiary centre. Methods: Retrospective study of the records of all children (<18 years) with nephrolithiasis diagnosis between 2008-17. Clinical features, etiology, recurrence, treatment, and outcomes were evaluated and compared throughout the study period through two equal periods (2008-12 versus 2013-17). Results: We identified 80 cases: isolated nephrolithiasis (86%) and associated with nephrocalcinosis (14%). Mean follow-up was 36 months (14-120). Median age at presentation was 8.6 years [3 months - 17 years]: 21% < 2 years-old and 46% ≥ 10 years. The annual ratio of referrals for nephrolithiasis increased on average 1.2% per year [0.3-11.8%]. Multiple etiological factors were present in 34%. A metabolic abnormality was identified in 54%: hypocitraturia (34%), hypercalcuria (24%), hyperoxaluria (15%), hyperuricosuria (15%) and cystinuria (1%), without age predominance (p=0.2). Urinary tract infection (24%) was the next most significant etiology and was more frequent below 2 years of age (p=0.001) and associated with struvite calculi (p=0.033). Median age at diagnosis was significantly lower in the studys first half (5 vs 10 years; p=0.019) and an infectious etiology was more frequent (p=0.043). In a logistic-regression analysis, a family history of nephrolithiasis was associated with a metabolic cause (p<0.01). Sixty-three percent became stone free and 24% had recurrence. Discussion: Nephrolithiasis new referrals gradually increased throughout the study period. The most common etiology was metabolic, which is usually responsible for nephrolithiasis appearance and its recurrence, emphasizing the need for a complete evaluation.

Kidney diseases with ocular involvement: a systematic review

Chronic kidney disease is an emerging health problem worldwide. The eye shares striking structural, developmental, and genetic pathways with the kidney, suggesting that kidney and ocular disease may be closely linked. The aim of this paper, beyond exploring the underlying pathogenic mechanisms and common risk factors, is a review of the main diseases with ocular and renal involvement.

Cellular origin and regulation of kidney fibrosis

Myofibroblasts take a key position as fibrosis driving, matrix secreting cells in kidney fibrosis and are thought to be important therapeutic targets in chronic kidney disease (CKD). However, their origin and activation pattern have been discussed for many years and are still partly unclear. Recently, Gli1+ cells, which reside in the perivascular niche, have been identified as progenitors of fibrosis-causing myofibroblasts. However, Gli1+ cells only account for about 50% of the myofibroblast population and are predominantly located in the kidney medulla. Nevertheless, the data suggests that Gli1+ cells are an important therapeutic target in kidney fibrosis since genetic ablation of these cells significantly ameliorates kidney fibrosis in rodents. Other potential sources of myofibroblasts in the kidney are circulating bone-marrow derived cells, endothelium and epithelium. The current review will discuss the cellular origin of myofibroblasts and potential mechanisms of myofibroblast activation driving fibrosis and CKD.

Immunoglobulin G4-related disease mimicking multiple myeloma

Immunoglobulin G4-related disease (IgG4-RD) is a rare, poorly understood immune mediated disorder. It is characterized by a wide clinical spectrum depending on the organs affected. Serum IgG4 may be elevated, but this is not mandatory. Imaging abnormalities are usually detected in the affected organs, which typically show enlarged dimensions. Definitive diagnosis is made upon tissue biopsy demonstrating lymphoplasmacytic infiltration with predominance of polyclonal IgG4-positive plasma cells, storiform fibrosis and obliterative phlebitis. The most common renal manifestations [(IgG4-related kidney disease (IgG4#8209;RKD)] include tubulointerstitial nephritis, membranous glomerulonephritis and pyelitis. There is, usually, good therapeutic response to corticosteroids, but rituximab may be needed in cases of relapsing or resistant disease. A diagnostic challenge, and because it diagnosis needs specific immunohistochemical staining techniques, IgG4-RKD should be contemplated in the differential diagnosis of obscure kidney disease in order not to be missed.

Light chain deposition disease: atypical associations in a rare disease

Light chain deposition disease is a systemic disorder characterized by deposition of monoclonal light chains in various organs. We present a case of a 58#8209;year#8209;old woman who was referred for a nephrology consultation due to worsening renal function and nephrotic range proteinuria. The diagnosis work#8209;up mentioned a plasmatic creatinine of 1.5mg/dL (estimated glomerular filtration rate of 38 mL/min/1.73m2 by MDRD equation), a urinary sediment with microhematuria, a protein/creatinine ratio of 5, a seric and urinary immunoelectrophoresis compatible with a monoclonal gammopathy IgG/Kappa, hypocomplementemia, type II cryoglobulinemia and a pulmonary nodule of irregular shape 15mm in diameter. A renal biopsy was performed and showed a marked expansion of the mesangium with nodules of amorphous material and small outbreaks of tubular atrophy associated with interstitial fibrosis. The nodules were PAS positive and Congo red negative and stained for light chain kappa by immunocytochemistry. Immunofluorescence was negative for IgA, IgG, IgM, C1q and C3c. A diagnosis of light chain deposition disease was made and concomitant multiple myeloma excluded. Treatment was initiated with bortezomib, dexamethasone and thalidomide with complete hematological remission and improvement in renal function. She also showed normalization of the cryoglobulinemia and disappearance of the pulmonary nodule previously detected, despite worsening of cardiac function as a result of the chemotherapy implemented. This clinical case highlights the well-known renal involvement in light chain deposition disease, but also some atypical clinical associations, namely type II cryoglobulinemia and pulmonary nodule disease.

Intestinal obstruction in a patient on chronic hemodialysis

Encapsulating peritoneal sclerosis (EPS) is an uncommon but serious complication of peritoneal dialysis (PD). We present a case report of EPS and a brief description of the disease. A previously stable 47-year-old male patient on hemodialysis (HD) presented to the hospital with weight loss, fever, anorexia, increased abdominal volume, anemia, increased inflammatory markers, septated hemoperitoneum, and peritoneal thickening on imaging. The patient had previously been on PD for 8 years and had 7 peritonitis episodes caused by different microorganisms. Note that the patient had a previous history of multiple vascular access failure and presented poor habitational conditions and socioeconomic status. He had been transferred from PD to HD five months earlier due to hypervolemia. A diagnosis of EPS was considered. Treatment was initiated with regular peritoneal lavage, nutritional support, oral prednisolone, and tamoxifen. The patient presented complete resolution of the symptoms and regularization of inflammatory markers. Two months later he presented to the emergency room with intestinal obstruction, and surgical enterolysis with debridement of the thick cocoon of fibrous tissue was performed. However, the patient presented several complications and died two months after admission. In conclusion, a high index of clinical suspicion of EPS in susceptible patients is necessary as the disease is infrequent and may be fatal. A greater awareness of EPS may lead to earlier or increased diagnosis rates in milder cases. This case report highlights the importance of implementing preventive measures in patients with several risk factors for EPS and considering an EPS diagnosis in a patient that is no longer on PD

Arterio-arterial graft - an option for hemodialysis patients with exhaustion of venous patrimony

Introduction: Vascular access (VA) for hemodialysis (HD) is the lifeline for End Stage Renal Disease (ESRD) patients. Long-term HD patients often have exhaustion of their venous patrimony for an autologous VA construction and, sometimes, even for a central venous catheter (CVC) placement. Case report: We describe the case of a 43-year-old woman with ESRD due to lupus nephritis, on maintenance HD since 2009. She also had secondary antiphospholipid syndrome and was chronically anticoagulated. Nevertheless, the patient had multiorgan thrombotic events (without sequelae) and several episodes of irreversible thrombosis of arteriovenous fistulas. Her HD course was also marked by multiple severe CVC infections, at different locations; a hemoperitoneum during cholecystectomy, and an immediate thrombosis of the renal artery of a kidney transplant. She was admitted to our hospital after an irreversible dysfunction of a right jugular CVC, with documentation of thrombosis of the superior and inferior vena cava. Exhaustion of the venous patrimony for HD was assumed and it was decided to make an arterio-arterial graft (AAG) of early cannulation. The first cannulation of the AAG was performed two days after surgical intervention, with no complications. The patient performed a twelve hour per week HD treatment with good efficiency. Conclusion: AAG is an alternative for HD patients who have exhausted all their venous patrimony and it can be considered prior to the placement of a CVC as their sole remaining vascular access.

What seems most likely may not be the case