Decline in glomerular filtration rate during pre-dialysis phase and survival on chronic renal replacement therapy.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is widely used in follow-up and assessment of patients before start of chronic renal replacement therapy (RRT). Reported data on impact of eGFR decline pattern during pre-dialysis phase on consequent survival on RRT are, however, non-existent. METHODS: Using the database of the Finnish Registry for Kidney Diseases, we conducted a cohort study of all incident adult patients (n = 457) entering chronic RRT in Finland in 1998, with follow-up until 31 December 2008. We included those (n = 319) with three serum creatinine measurements (at ∼12 and 3 months and 1 to 2 weeks prior to RRT start) and calculated their slopes of eGFR using the modification of diet in renal disease formula. According to eGFR slopes (in mL/min/1.73m(2)/year), patients were divided into tertiles: most rapid (>8.5, n = 107), intermediate (3.4-8.5, n = 107) and slowest decline (<3.4, n = 105). RESULTS: Median survival time was 5.6 (95% confidence interval 4.2-7.0) years. Compared to the patient group with the slowest eGFR decline, age- and gender-adjusted relative risk of death was 1.1 (0.8-1.5) in the intermediate group and 1.7 (1.2-2.4, P = 0.002) in the most rapid decline group. When further adjusting for kidney disease diagnosis, comorbidities, use of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, body mass index, blood haemoglobin and serum albumin, the association was no longer significant. CONCLUSIONS: Rapid decline in eGFR before entering chronic RRT associates with increased mortality on RRT. The elevated mortality appears to be caused by known risk factors for death on RRT.

Teriparatide treatment complicated by malignant myeloma.

Recombinant human parathyroid hormone (1-34) (rhPTH 1-34), teriparatide (Forsteo in Europe), is a new compound that has been introduced and shown to be successful in the treatment of osteoporosis. The mechanisms of action include a pulsative influence on the RANKL/OPG system resulting in osteoblast activation and increased bone formation by teriparatide. In malignant myeloma there is an imbalance between osteoclast and osteoblast activity with involvement of the RANKL/OPG system among others. We report a case with monoclonal gammopathy of uncertain significance (MGUS) who developed malignant myeloma after teriparatide treatment and we suggest that in addition to malignant myeloma and smouldering myeloma, MGUS should also be considered contraindicated for teriparatide treatment.

Primary osteosarcoma of the right heart ventricle and atrium; a case report.

Most primary malignancies of the heart, among them also osteosarcoma are found in the left and very uncommonly in the right ventricle. We report a 75-year-old patient with a primary osteosarcoma sited in the right ventricle occluding the pulmonary outflow. The diagnosis was made when the patient was alive, using echocardiography and computerized scan tomography examinations. Like in previous reports on such malignancies, it was far too late for surgical or other therapeutic interventions, and the histological diagnosis was made post mortem.

Forty years abuse of baking soda, rhabdomyolysis, glomerulonephritis, hypertension leading to renal failure: a case report.

We present a patient who had ingested sodium bicarbonate for treatment of alcoholic dyspepsia during forty years at increasing doses. During the last year he had used more than 50 grams daily. He presented with metabolic alkalosis, epileptic convulsions, subdural hematoma, hypertension and rhabdomyolysis with end stage renal failure, for which he had to be given regular intermittent hemodialysis treatment. Untreated hypertension and glomerulonephritis was probably present prior to all these acute incidents. Examination of the kidney biopsy revealed mesangial proliferative glomerulonephritis and arterial wall thickening causing nephrosclerosis together with interstitial calcinosis. The combination of all these pathologic changes might be responsible for the development of progressive chronic renal failure ending up with the need for continuous intermittent hemodialysis treatment.

Malignant myeloma in a patient after treatment for osteoporosis with teriparatide; a rare coincidence.

A breakthrough in understanding of mechanisms of bone structure regulation has brought about the introduction of the new synthetic recombinant human parathyroid hormone 1-34 (PTH1-34; Teriparatide) in the treatment of osteoporosis. These mechanisms, involving the RANKL, RANK, and osteoprotegerin system, are also known to be involved in malignant myeloma (MM) and tumor and bone metastasis development. We report a case in which MM was found after treatment of osteoporosis with teriparatide. We were unable to demonstrate any direct association between the MM and teriparatide treatment. However, it seemed intriguing that similar mechanisms are activated in the development of MM as those being working during teriparatide treatment. In the view of our case, we propose that MM by examination of serum protein fraction should be searched for prior to treatment with teriparatide as it is an exclusion criterion in teriparatide treatment of secondary osteoporosis. A search for other metastatic diseases prior to teriparatide treatment should eventually also be considered. The theoretical basis for our proposal is discussed.

Mesangial proliferative glomerulonephritis after autologous stem cell transplantation.

Although glomerulonephritis and renal failure have been observed after allogenic stem cell transplantation, only a few such reports were published about patients undergoing autologous stem cell transplantation. We report a case of mesangial proliferative glomerulonephritis developing 4 months after autologous stem cell transplantation for chronic lymphatic leukemia. Serological test results, together with histological, immunohistochemical, and electronic microscopic findings of a kidney biopsy specimen, confirmed the diagnosis of mesangial proliferative glomerulonephritis in our patient. Complement and immunoglobulin A were not present in the kidney biopsy specimen. An abnormal clone, not previously reported, with the translocation t(5;11)(q31;q13) in blood and bone marrow was observed. The reason for and whether progenitor cells in stem cell transplantations could contribute to the development of glomerulonephritis remain open questions. Kidney biopsy should be performed in patients with microscopic hematuria and/or proteinuria after autologous stem cell transplantation.

Pirfenidone and candesartan ameliorate morphological damage in mild chronic anti-GBM nephritis in rats.

BACKGROUND: The antifibrotic substance pirfenidone and the angiotensin II type I receptor antagonist candesartan cilexetil, given alone and in combination, were tested in rats with chronic anti-glomerular basement membrane glomerulonephritis (anti-GBM GN). METHODS: Male Wistar rats with anti-GBM GN were treated for 8 weeks with candesartan (4 mg/kg body weight/day), pirfenidone (500 mg/kg body weight/day) or a combination of both drugs. One GN group received no treatment and untreated non-GN-rats were used as controls. Blood pressure and urinary protein excretion were measured after 3 and 7 weeks. Kidney histology was complemented by ultrastructural investigation and by quantification of collagen Ialpha mRNA. RESULTS: The percentage of glomeruli with adsorption droplets in podocytes correlated well with the amount of proteinuria (r = 0.873, P<0.01) and was significantly lowered in rats treated with candesartan (8.3 vs GN 24.6%), pirfenidone (9.8%) and combined treatment (2.6%, P<0.05 vs candesartan alone). A comparable lowering was seen for segmental sclerosis (GN 11%, candesartan 0.7%, P<0.05 vs GN, pirfenidone 1.8%, P = 0.09 vs GN, candesartan/pirfenidone 0.1%, P>0.5 vs candesartan alone). Cortical collagen Ialpha mRNA expression was significantly decreased in all treatment groups. Ultrastructural investigation showed an amelioration of basement membrane alterations and podocyte damage in the treatment groups. Candesartan caused significant blood pressure reduction and the effect was significantly enhanced by combination therapy after 3 weeks. Rats treated with pirfenidone showed blood pressure values similar to control rats. CONCLUSION: Pirfenidone has a beneficial effect on morphological changes in anti-GBM GN comparable with candesartan although with a trend to slightly better results with candesartan treatment. Moreover, our results suggest an additive effect of combination treatment.