Mineral bone disorder and osteoporosis in hemodialysis patients.

BACKGROUND: Bone disease is common in patients undergoing hemodialysis. It is the result of bone turnover abnormalities and the decrease of bone mineral density (BMD). We aimed to determine the usefulness of serum bone turnover markers and BMD measurement by dual-energy x-ray absorptiometry (DXA) in hemodialysis patients. METHODS: We conducted a cross-sectional study including 90 hemodialysis for more than 12 months. Bone mineral density was assessed by DXA. Peripheral blood samples were obtained from each patient before dialysis in a fasting state within a week of the DXA. Biochemical variables of calcium and phosphate were measured. One bone formation marker (bone-specific alkaline phosphatase (bAP), one bone resorption marker (carboxy-terminal telopeptides of type 1 collagen (CTX)) were measured. Total alkaline phosphatase (TAP), intact parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) which is a bone-derived hormone were also measured. RESULTS: CTX values were 6.25 times higher than the normal limit of the assay. Bone alkaline phosphatase levels were less than 10 ng/mL in 28.8% of cases. 23% of patients have osteoporosis and 45% have osteopenia. Femoral BMD had negative correlations with age and PTH levels. FGF23 levels were significantly increased in patients with osteoporosis affecting the lumbar. The levels of bAP and CTX showed a positive correlation. Both circulating bAP and CTX levels showed also positive correlations with PTH levels. Fractures, observed in 12.2% of cases, were associated with low PTH values and the existence of osteoporosis. CONCLUSIONS: Our study showed that osteoporosis and fracture are common in dialysis patients. The reduced BMD was associated with advanced age and elevated levels of PTH. Markers of bone turnover and FGF23 may play a role in the diagnosis of bone disease in hemodialysis patients. DXA measurement is necessary for the monitoring for bone loss.

Mineral bone disorder and osteoporosis in hemodialysis patients

Abstract Background: Bone disease is common in patients undergoing hemodialysis. It is the result of bone turnover abnormalities and the decrease of bone mineral density (BMD). We aimed to determine the usefulness of serum bone turnover markers and BMD measurement by dual-energy x-ray absorptiometry (DXA) in hemodialysis patients. Methods: We conducted a cross-sectional study including 90 hemodialysis for more than 12 months. Bone mineral density was assessed by DXA. Peripheral blood samples were obtained from each patient before dialysis in a fasting state within a week of the DXA. Biochemical variables of calcium and phosphate were measured. One bone formation marker (bone-specific alkaline phosphatase (bAP), one bone resorption marker (carboxy-terminal telopeptides of type 1 collagen (CTX)) were measured. Total alkaline phosphatase (TAP), intact parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) which is a bone-derived hormone were also measured. Results: CTX values were 6.25 times higher than the normal limit of the assay. Bone alkaline phosphatase levels were less than 10 ng/mL in 28.8% of cases. 23% of patients have osteoporosis and 45% have osteopenia. Femoral BMD had negative correlations with age and PTH levels. FGF23 levels were significantly increased in patients with osteoporosis affecting the lumbar. The levels of bAP and CTX showed a positive correlation. Both circulating bAP and CTX levels showed also positive correlations with PTH levels. Fractures, observed in 12.2% of cases, were associated with low PTH values and the existence of osteoporosis. Conclusions: Our study showed that osteoporosis and fracture are common in dialysis patients. The reduced BMD was associated with advanced age and elevated levels of PTH. Markers of bone turnover and FGF23 may play a role in the diagnosis of bone disease in hemodialysis patients. DXA measurement is necessary for the monitoring for bone loss.(AU)

Determinants of patency of arteriovenous fistula in hemodialysis patients.

The arteriovenous fistula (AVF) is the vascular access of the first choice for hemodialysis (HD). Studies on patency of AVF and its affecting factors reveal a high risk for access failure. The aim of this study was to assess the primary and secondary AVF patency and their determinant factors. It was a retrospective, descriptive study conducted in the HD facility of the Nephrology Department in Rabta University Hospital. We included AVF created before December 2009 in end-stage renal disease (ESRD) patients. The end of the follow-up was fixed in December 2013. We included 126 AVFs created in 111 patients; 22.5% were aged >65 years, 39.6% were diabetic, 68.5% were hypertensive, and 26.1% had peripheral vascular disease. The primary patency rates were 78% at one year and 42% at five years. The secondary patency rates were 80% at one year and 69% at five years. Multivariate analysis revealed that the factors affecting the primary patency of AVF were: the use of jugular catheter for longer than three months (odds ratio (OR):1.91, P = 0.044) and a C-reactive protein >5 mg/L (OR: 1.7, P = 0.049). Aging (>65 years) (OR: 2.46, P = 0.042), referral time to a nephrologist <6 months before onset of ESRD (OR: 2.87, P = 0.015), absence of an antiplatelet therapy (OR: 4.47, P = 0.005), and serum phosphorus <45 mg/L (OR: 2.07, P = 0.045) were the significant impairing risk factors for secondary AVF patency. Our study suggests that early referral and creation of AVF and maturation before ESRD as well as its adequate monitoring are essential for maintaining patency.

Kidney involvement in Crow-Fukase syndrome.

Crow-Fukase syndrome, also known as POEMS syndrome, is a rare plasma dyscrasia characterized by monoclonal gammopathy and various combinations of polyneuropathy, organomegaly, endocrinopathy and dermatological changes, and their initials stand for the acronym POEMS. Substantial kidney involvement is rarely related to this disease. Our report is about five patients suffering from the POEMS syndrome with kidney involvement that rapidly progressed to end-stage renal disease. Our report is about three females and two males with a mean age of 60.6 years. Neuropathy was noted in all the cases. Endocrinopathy included hypothyroidism and/or diabetes. Skin changes were noted in one case, and included peri-orbital hyperpigmentation. Monoclonal gammopathy was present in all the cases and was related to multiple myeloma in three cases. Kidney involvement presented in all the five cases. Treatment included Melphalan, Thalidomid, steroids and hemodialysis. Survival was short for three patients, from five to 34 months.

Therapeutic efficacy of a biosimilar epoetin alfa in hemodialysis patients.

Anemia is a frequent complication in patients with chronic kidney disease. However, human recombinant erythropoietin (rHu-EPO) has revolutionized the management of anemia in chronically dialyzed patients. Epomax ® is a new rHu-EPO alfa manufactured in Tunisia (Medis Laboratories). The aim of this study was to evaluate the efficacy and tolerance of Epomax ® in chronic hemodialysis (HD) patients in a phase-III, multicenter, clinical trial. Fiftythree HD patients (mean age 47.7 ± 13 years) who received a stable dose of rHu-EPO (Hemax ® , a rHu-EPO alfa manufactured by Biosidus Laboratories) subcutaneously were switched to Epomax ® via the same route of administration. At baseline, the mean systolic pressure was 132 ± 18 mm Hg and the mean diastolic pressure was 79 ± 8 mm Hg. The mean blood hemoglobin was 10.2 g/dL and the median ferritin level was 667 ng/mL. After a follow-up of 43 days, the mean blood hemoglobin was 10.5 g/dL under the effect of Epomax ® . There was no significant difference in the mean hemoglobin levels between the treatments with both drugs. Few adverse events were reported during the study. We conclude that Epomax ® was effective at maintaining the hemoglobin levels at target concentrations and was well tolerated in HD patients.

Renal paraneoplastic vasculitis complicating lung adenocarcinoma.

Renal paraneoplastic vasculitis (RNPV) is rare. It can be revealed by glomerulonephritis, microaneurysms or renal failure. RPNV may precede the onset of the primary tumor, and treatment and prognosis depend on the etiology (primary tumor). A 54-year-old man who had a primary lung adenocarcinoma was admitted for nephrotic syndrome. The investigations revealed RNPV. The patient was treated with corticosteroids at high dose and cyclophosphamide with improvement of the renal condition; however, the patient died from worsening of his pulmonary neoplasia.

Subcutis calcinosis caused by injection of calcium-containing heparin in a chronic kidney injury patient.

Subcutis calcinosis, characterized by abnormal calcium deposits in the skin, is a rare complication of using calcium-containing heparin occurring in patients with advanced renal failure. We report the case of an 83-year-old female, a known case of chronic kidney disease (CKD) for four years with recent worsening of renal failure requiring hospitalization and hemodialysis. She developed subcutis calcinosis following injection of calcium-containing heparin. Biochemical tests showed serum parathormone level at 400 pg/dL, hypercalcemia, elevated calcium-phosphate product and monoclonal gammopathy related to multiple myeloma. She developed firm subcutaneous nodules in the abdomen and the thighs, the injection sites of Calciparin ® (calcium nadroparin) that was given as a preventive measure against deep vein thrombosis. The diagnosis of subcutis calcinosis was confirmed by the histological examination showing calcium deposit in the dermis and hypodermis. These lesions completely disappeared after discontinuing calcium nadroparin injections. Subcutis calcinosis caused by injections of calcium-containing heparin is rare, and, to the best our knowledge, not more than 12 cases have been reported in the literature. Pathogenesis is not well established but is attributed to the calcium disorders usually seen in advanced renal failure. Diagnosis is confirmed by histological tests. Outcome is mostly favorable. The main differential diagnosis is calciphylaxis, which has a poor prognosis. Even though rarely reported, we should be aware that CKD patients with elevated calcium-phosphorus product can develop subcutis calcinosis induced by calcium-containing heparin. When it occurs, fortunately and unlike calciphylaxis, outcome is favorable.

Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.

Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

Kaposi's sarcoma with HHV8 infection and ANCA-associated vasculitis in a hemodialysis patient.

The association between Kaposi's sarcoma (KS) and human herpes virus eight (HHV-8) infection is rarely reported in hemodialysis (HD) patients. We report here the rare association of KS, HHV-8 and hepatitis C virus (HCV) infection as well as syphilis in a HD patient. We report the case of a 72-year-old woman who presented with microscopic polyangiitis with alveolar hemorrhage and pauci-immune necrosing and crescentic glomerulonephritis as well as renal failure requiring HD. Biological tests showed positive HCV and syphilis tests. The patient was treated by HD and intravenous pulse, followed by oral corticosteroids and six cyclophosphamide monthly pulses with remission of the alveolar hemorrhage, but without renal functional recovery as the patient remained HD dependent. Five months after the first treatment administration, she developed extensive purpuric lesions on her lower limbs, abdomen face and neck. A skin biopsy showed KS. The HHV-8 test was positive, with positive polymerase chain reaction-HHV8 in the serum and skin. After immunosuppression withdrawal, the KS skin lesions regressed rapidly without relapse after 12 months of follow-up, but alveolar hemorrhage relapsed after 16 months of follow-up. Our case showed that the immunosuppressed state related to multiple factors such as aging, vasculitis, HHV-8, HCV, syphilis, immunosuppressive therapy and HD may all have contributed to the development of KS in our patient.

Alveolar hemorrhage and kidney disease: characteristics and therapy.

Anti-neutrophil cytoplasmic antibody-associated vasculitis and Goodpasture's glomerular basement membrane disease are the most common causes of diffuse alveolar hemorrhage, a life-threatening disease. Systemic lupus erythematosus and the antiphospholipid syndrome are also causes of alveolar hemorrhage. We retrospectively reviewed 15 cases of diffuse alveolar hemorrhage (DAH) associated with renal diseases. Diagnosis of DAH was based on the presence of bloody bronchoalveolar lavage fluid. There were three men and 12 women, with a mean age of 50.5 years (extremes: 24-74 years). Proteinuria and hematuria were observed, respectively, in 15 and 14 cases. Six patients revealed arterial hypertension. Crescentic glomerulonephritis was diagnosed with kidney biopsies in ten cases. The etiology of renal disease was microscopic polyangiitis (MPA) in seven cases, Wegener disease in four cases, systemic lupus erythematous in one case, cryoglobulinemia in one case, myeloma in one case and propyl-thiouracil-induced MPA in one case. Hemoptysis occurred in 14 cases. The mean serum level of hemoglobin was 7.1 g/dL (5.1-10 g/dL). The mean serum creatinine concentration was 7.07 mg/dL (2.4-13.7 mg/dL). Gas exchange was severely compromised, with an oxygenation index <80 mmHg in 14 patients and <60 mmHg in seven patients. Bronchoalveolar lavage was performed in 11 cases, and had positive findings for hemorrhage in all. Methylprednisolone pulses and cyclophosphamide were used in 14 patients. Plasmapheresis was performed in three cases. One patient received cycles of Dexamethasome-Melphalan. Three patients died as a result of DAH. The mortality rate in our study was 20%.

Value of electron microscopy in the diagnosis of glomerular diseases.

To evaluate the contribution of electron microscopy to the final diagnosis of glomerulopathies, the authors established a prospective study during the first semester of 2006. A total of 52 kidney biopsies were performed with 3 samples for light microscopy, immunofluorescence, and electron microscopy. Among these renal biopsies, only 20 were examined with electron microscopy because the diagnosis made on the basis of conventional methods had remained unclear or doubtful. In 18 cases, electron microscopy was undertaken for the investigation of primary kidney disease. The 2 remaining cases were transplant biopsies. In this series of 20 patients, there were 3 children with an average age of 9 years and 17 adults with an average age of 35.5 years. Fifteen patients (75%) were nephrotic. The study revealed that electron microscopy was essential for diagnosis in 8 cases (40%) and was helpful in 12 cases (60%). In conclusion, the results showed that the ultrastructural study provides essential or helpful information in many cases of glomerular diseases, and therefore electron microscopy should be considered an important tool of diagnostic renal pathology. As was recommended, it is important to reserve renal tissue for ultrastructural study unless electron microscopy can be routinely used in all biopsies. Thus, this technique could be performed wherever a renal biopsy has to be ultrastructurally evaluated.

[Pheochromocytoma in end-stage renal disease patient treated by peritoneal dialysis]. / Phéochromocytome surrénalien chez un insuffisant rénal chronique en dialyse péritonéale.

Pheochromocytoma is a rare tumor responsible for paroxysmal hypertension which is difficult to control. Diagnosis is important because it represents a curable form of hypertension. Few cases of pheochromocytoma patients with end-stage renal failure were reported in the literature. These cases are specially responsible for diagnosis and therapeutic problems. We report here a case of an end-stage renal failure patient who has pheochromocytoma, he was treated by automated peritoneal dialysis. The patient is a 47-year-old man who has an IgA glomerulonephritis. On peritoneal dialysis, his blood pressure level remains high despite four antihypertensive drugs association and adequate dialysis. Furthermore, the patient suffered from headaches, sweats and palpitations. This leads to suspect pheochromocytoma. Thus, urinary excretion rates of metanephrines and normetanephrines were high. Radiographic diagnosis tests were negative but MIBG scintigraphy was able to localise the tumor in the left suprarenal gland. He had coelioscopic left adrenalectomy without complications, microscopic studies showed an hyperplasia of the adrenal medulla. Soon after surgery his blood pressure was well controlled by one antihypertensive drug. We conclude that refractory hypertension, as a possible diagnosis, is uncommon in peritoneal dialysis patients. Pheochromocytoma must be eliminated by careful evaluation.

Bleeding and thrombosis in a patient with secondary antiphospholipid syndrome.

Antiphospholipid antibodies have been associated with occurrence of arterial and venous thrombotic events and fetal loss, which together constitute the antiphospholipid syndrome (APS). However, bleeding is rare in this syndrome. We report a case of systemic lupus erythematosus (SLE) with APS complicated simultaneously by thrombotic and hemorrhagic events. A 34-year-old woman was a known case of diffuse proliferative lupus nephritis associated with APS, on treatment with corticosteroids, cyclophosphamide and anticoagulants. She presented in February 2004 with severe anemia, menorrhagia, gingival bleeding and acute loss of vision in the left eye. Investigations revealed a hematoma in the psoas muscle with thrombosis of the inferior vena cava and occlusion of the retinal vein. Blood tests revealed a strongly positive lupus anticoagulant, factor XI deficiency (35%) and decrease of free protein S (44%). Factor XI inhibitor, anti-prothrombin, and anti-protein S antibodies were absent. The patient was treated with corticosteroids and six pulses of cyclophosphamide, which resulted in a rapid disappearance of bleeding, reduction of hematoma and normalization of hematological abnormalities. She was maintained on corticosteroids, azathioprine and anticoagulant agents were introduced. After a follow-up of 28 months, there was no recurrence of bleeding, the thrombosis had resolved, and there was a decrease in the levels of circulating anticoagulant as well as anticardiolipin antibodies.

Interstitial and glomerular renal involvement in sarcoidosis.

Sarcoidosis is a systemic disease characterized by chronic granulomatous inflammation. Chronic kidney disease (CKD) was reported in less than 1% of patients of sarcoidosis. The prevalence of tubulo-interstitial nephritis (TIN) in sarcoidosis varies from 7 to 27%. In this retrospective study, we present 15 patients with interstitial or glomerular renal involvement secondary to sarcoidosis diagnosed in our center from 1975 to 2006. Patients were 13 (96.6%) females and two males with a mean age of 56.5 years. CKD was present in 14(93.3%) patients, proteinuria in 13(96.6%), and nephrotic syndrome in one. Pulmonary involvement was present in 10 (66.6%) patients. Renal biopsy performed in 12 (80%) patients revealed TIN lesions in 10 (66.6%) patients, extracapillary proliferative glomerulonephritis (GN) in one, and membranous GN type 2 in another. Corticosteroid therapy using prednisolone 0.5 to 1 mg/kg per day was used in 12(80%) patients. Ten (66.6%) patients were followed up for a mean period of 25 months (ranged from 2 to 48 months). The outcome was favorable with 7 (46.6%) patients improved their renal function, 6 (40%) remained with a moderate CKD, one normalized his renal function, and one died suddenly after 2 months of initiating the treatment corticosteroids. We conclude that corticosteroid treatment is efficient in TIN and variably efficient in GN. Patients with sarcoidosis may cause advanced renal failure, which renders it a serious nephrological condition.

Chronic subdural haematoma and autosomal polycystic kidney disease: report of two new cases.

Chronic subdural haematoma (SDH) was recently described in some patients who were suffering from autosomic dominant polycystic kidney disease (ADPKD). It results in various neurological symptoms mimicking those related to intracranial aneurysms, which are relatively frequent in such patients. The authors report two cases of chronic SDH observed in two patients known to have advanced renal failure attributed to ADPKD. Medical imaging failed to reveal features of associated intracranial abnormalities such as aneurysms or arachnoid cysts. Surgical drainage resulted in a good recovery without relapse during a long period of follow up that exceeded 10 years in the first case.