Gitelman syndrome: consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Gitelman syndrome (GS) is a rare, salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria. The disease is recessively inherited, caused by inactivating mutations in the SLC12A3 gene that encodes the thiazide-sensitive sodium-chloride cotransporter (NCC). GS is usually detected during adolescence or adulthood, either fortuitously or in association with mild or nonspecific symptoms or both. The disease is characterized by high phenotypic variability and a significant reduction in the quality of life, and it may be associated with severe manifestations. GS is usually managed by a liberal salt intake together with oral magnesium and potassium supplements. A general problem in rare diseases is the lack of high quality evidence to inform diagnosis, prognosis, and management. We report here on the current state of knowledge related to the diagnostic evaluation, follow-up, management, and treatment of GS; identify knowledge gaps; and propose a research agenda to substantiate a number of issues related to GS. This expert consensus statement aims to establish an initial framework to enable clinical auditing and thus improve quality control of care.

Anakinra is a possible alternative in the treatment and prevention of acute attacks of pseudogout in end-stage renal failure.

We describe the case of a 71-year-old man with recurrent pseudogout attacks affecting multiple joints. He had end-stage renal failure that contra-indicated the use of non-steroidal anti-inflammatory drugs and was resistant to therapy with glucocorticoids. Based on the recent findings that interleukin (IL)-1beta is involved in crystal-induced inflammation, the patient received anakinra, a specific IL-1 inhibitor, in order to treat an acute attack of pseudogout. In addition, anakinra was administered as preventive therapy 3days per week after each hemodialysis session. Under this treatment, he did not present any severe episode of arthritis after a follow-up of 8 months. This observation suggests that anakinra is efficacious and safe for the prevention of crystal-induced arthritis in patients with severe renal failure.

Inhibition of alkaline phosphatase by cysteine: implications for calcium pyrophosphate dihydrate crystal deposition disease.

OBJECTIVE: Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease, a common arthritis affecting the elderly, is characterized by the deposition of CPPD crystals in articular joints. The mechanism underlying disease expression is unknown, but factors contributing to the pathogenesis may involve changes in enzymatic activities involving pyrophosphate and phosphate metabolism. Tissue nonspecific alkaline phosphatase (TNAP) is one of the major enzymes regulating pyrophosphate concentrations in articular joints. We hypothesized that inhibition of TNAP activity at pH = 7.4 by endogenous molecules can lead to CPPD disease pathogenesis. METHODS: We investigated the inhibitory effects of the amino acid cysteine on TNAP's phosphatase, inorganic pyrophosphatase, and CPPD crystal dissolution activities. Kinetic parameters V(max), K(M), concentration for 50% inhibition (I(50)), inhibitor constant (K(I)), and specific activities calculated from Initial Velocity, Eadie-Hofstee, Simple, Dixon, and Secondary plots were used to assess enzyme inhibition. RESULTS: Cysteine inhibited TNAP's phosphatase activity uncompetitively and its inorganic pyrophosphatase activity mix-competitively. CPPD crystal dissolution activity was also inhibited. I(50) values demonstrated that high cysteine concentration is required to inhibit 50% of enzyme activity. K(I) values suggested that inorganic pyrophosphatase activity is inhibited more than the phosphatase activity. Ca(++) and Mg(++) ion concentrations may regulate this inhibition. CONCLUSION: The control of endogenous inhibitors, such as cysteine, that interfere with TNAP's ability to regulate CPPD crystal formation and dissolution in joints could be a potential therapeutic option for CPPD crystal deposition disease.

[Post-parathyroidectomy pseudogout in primary hyperparathyroidism]. / Seudogota posparatiroidectomía en el hiperparatiroidismo primario.

We report two cases of pseudogout after parathyroidectomy by primary hyperparathyroidism. The pseudogout in each instance developed within 48 hours after parathyroid adenoma resection. Calcium supplement therapy, nonsteroidal anti-inflammatory drugs and colchicine (1 mg/day) suppressed the acute attack. The chondrocalcinosis is often asymptomatic or undiagnosed, for that, preoperative radiological studies of the knees, wrists and pelvis are recommended to screen for chondrocalcinosis. We advocate also, therapy with colchicine (1 mg/day, oral) in the prophylaxis of postoperative pseudogout.

[Primary hyperparathyroidism in elderly patients].

Retrospective analysis has been performed in 404 patients, undergoing initial operation for primary hyperparathyroidism for differences in clinical presentation, laboratory data, pathological findings and outcome of surgery. In elderly patients (> = 60 years of age, n = 116), neuromuscular and psychic symptoms, hypertension, cholelithiasis and pseudogout were significantly more common, while renal stones were less common than in younger patients. There were no significant difference in preoperative laboratory findings, parathyroid pathology and surgical cure rate. Parathyroidectomy could be safely performed under local anesthesia, particularly in elderly patients in whom general anesthesia was involved with an increased operative risk. An attack of pseudogout was the most common postoperative complication. Hence, immediate calcium supplementation after operation is recommended in patients with a radiologic finding of chondrocalcinosis.

Crise de pseudogota como complicaçäo após paratiroidectomia no hiperparatiroidismo primário / Pseudogout crisis as a post parathyroidectomy complications in the primary hyperparathyroidism

A pseudogota é um quadro agudo ou sub-agudo de artrite associada à presença de cristais de diidrato de pirofosfato de cálcio (DHPC) no espaço sinovial. Relaciona-se ao hiperparatiroidismo primário (HPP), principalmente quando da reduçao rápida da calcemia que ocorre após a paratiroidectomia, Relatamos o caso de uma paciente de 71 anos de idade internada em nosso serviço por apresentar dores ósseas e articulares difusas com duraçao de dois anos. Os exames laboratoriais mostraram cálcio total de 11,4 mg/dl (normal: 8,5 a 10,5 mg/dl), cálcio ionizado de 1,36 mmol/L (normal: 1,14 a 1,29 mmol/L) e paratormônio intacto de 279 pg/ml (normal: 10-70 pg/ml), tendo sido feito diagnóstico de HPP. As radiografias simples evidenciaram condrocalcinose em joelhos, cotovelos e punhos. Submetida a paratiroidectomia, que revelou hiperplasia das paratiróides, evoluiu com hipocalcemia no oitavo dia pós-operatório (cálcio ionizado de O,9 mmol/l) e no décimo-primeiro dia apresentou artrite em tornozelo esquerdo. A punçao articular mostrou líquido sinovial com numerosos cristais sugerindo pseudogota. Na evoluçao, houve melhora articular concomitante à normalizaçao da ca;cemia e ao uso de anti-inflamatório nao hormonai. Um mês depois foi observado recidiva da artrite em punho e cotovelo esquerdos concomitante a novo surto de hipocalcemia. Em resumo, a pseudogota é uma complicaçao importante em pacientes com HPP submetidos à paratiroidectomia. Na opiniao dos autores, por estar associada à hipocalcemia, a pseudogota pode ser prevenida mediante a suplementaçao precoce de cálcio e vitamina D no pós-operatório imediato.

Pseudogout associated with primary hyperparathyroidism: management in the immediate postoperative period for prevention of acute pseudogout attack.

Three cases of pseudogout associated with primary hyperparathyroidism are reported. Preoperative radiological studies revealed association of pseudogout. Considering the frequent development of acute pseudogout attack following parathyroidectomy, prevention of a sudden decrease in the serum calcium concentration was attempted using calcium supplement therapy starting on the first postoperative day in all three cases. Serum calcium slowly decreased to the normal range, and the postoperative courses were uneventful. From these experiences, we advocate that calcium supplement therapy is worth trying for the prevention of acute pseudogout attack following parathyroidectomy.

Colchicine prophylaxis in pseudogout.

Ten patients with recurrent attacks of pseudogout were followed for 1 year before and 1 year after receiving oral colchicine 0.6 mg BID. Thirty-two episodes of acute arthritis were recorded in the year (3.2/patient/year) before the start of the drug and only 10 while taking the drug (1/patient/year) (p less than 0.001). Ninety percent of the patients benefitted from the drug. Our study supports the effectiveness of oral colchicine as a prophylactic agent in recurring pseudogout.