Dermatan sulfate: an alternative to unfractionated heparin for anticoagulation in hemodialysis patients.

BACKGROUND: Unfractionated heparin (UFH) is the standard anticoagulant in regular dialysis treatments (RDTs), despite the fact that it may induce thrombocytopenia, dyslipidemia, allergy and osteoporosis. Dermatan sulfate (DS) selectively inhibits thrombin, does not inhibit F-Xa and does not interfere with platelets (PLTS). Here we described an original protocol for the use of DS as anticoagulant in RDT and compared its effects with those of UFH. METHODS: In 102 patients, 7,254 RDTs were performed using DS for anticoagulation (DS-phase) and 5,707 with UFH (UFH-phase). DS was supplied as initial bolus (80 ± 12 mg) and continuous infusion (14 ± 7 mg/hour). With UFH, the initial bolus was 1,475 ± 141 IU and continuous infusion 576 ± 349 IU/hour. Activated partial thromboplastin time and its ratio were measured at least monthly, both before (pre-RDT APTT ratio) and after (post-RDT APTT ratio) RDT sessions. With 41 of 102 patients, both DS and UFH doses were not changed during study phases (stable patients). In this subset, the coefficient of variation (CV) of all pre-RDT APTT ratio and post-RDT APTT ratio values was calculated. RESULTS: In DS and UFH phases, post-RDT APTT ratio increased by 61% and 50%, respectively, by comparison with pre-RDT APTT ratio (p<0.001). PLTS count was lower in the UFH than in the DS phase (p<0.01). In stable patients, post-RDT APTT ratio CV was lower in the DS than in the UFH phase (p<0.001), which indicates a more predictable anticoagulant effect of DS compared with UFH. CONCLUSIONS: DS appeared as effective as UFH for anticoagulation in RDT. It can reliably be considered as an alternative approach especially in cases of thrombocytopenia or other adverse effects of UFH.

[A case of hypercalcemia in hemodialysis]. / Un caso di ipercalcemia in emodialisi.

We report a case of hypercalcemia in a female patient who was restarted on hemodialysis 22 years after renal transplantation. Graft biopsy showed chronic post-transplant nephropathy. Treatment with immunosuppressants and steroids was maintained owing to residual graft function. She was then given oral paracalcitol 1 µg/d for secondary hyperparathyroidism (iPTH 850 pg/mL) and her transplant medication was reduced and then discontinued. After this, the patient referred widespread joint pain, especially in the hips and subsequently presented with erythema nodosum. She also developed hypercalcemia and hyperphosphatemia which persisted after stopping paracalcitol. The clinical picture of increased serum calcitriol, with depressed PTH, suggested sarcoidosis, despite normal ACE levels, a chest X-ray and skin biopsy confirmed the diagnosis, and the patient was started on prednisone 50 mg/day, resulting in prompt normalization of both symptoms and blood chemistry. This is a rare case of hypercalcemia secondary to sarcoidosis in an uremic patient. The sarcoidosis was most likely suppressed by the transplant therapy and rapidly developed after this was suspended. Prompt diagnosis resulted in a good therapeutic response.

Effects of dermatan sulfate for anticoagulation in continuous renal replacement therapy.

BACKGROUND: Dermatan sulfate (DS) is a natural glycosaminoglycan with a unique mechanism of action on the coagulation system. Unlike unfractionated heparin (UFH), DS selectively inhibits thrombin, does not inhibit factor Xa, is effective on both free and fibrin-bound thrombin and does not interfere with platelets. This study represents the first experience using DS as anticoagulant in patients on continuous renal replacement therapy (CRRT). METHODS: A total of 147 patients in our intensive care unit who developed acute renal failure after cardiovascular surgery were on CRRT according to the same protocol: machine, Gambro Prisma; filter, AN69, 0.9 m2; QB, 150 ml/min; QD, 2,000 ml/hour; and Q(Infusate), 500 ml/hour. In a retrospective cohort of 100 patients, anticoagulation was performed with UFH (UFH-CRRT): initial bolus of 530 +/- 363 IU, then i.v. infusion of 598 +/- 261 IU/hour. A prospective cohort of 47 patients received DS (DS-CRRT) as a 150-mg bolus followed by a 13.5 +/- 3 mg/hour infusion. Hematology tests were performed at baseline and during CRRT; filter lifetime was measured from the start to filter clotting. RESULTS: Median filter lifetime was 58 hours in DS-CRRT vs. 47 hours in UFH-CRRT (p<0.001). No differences emerged in basal hematology and hemostasis tests between groups. During CRRT, DS produced a smaller activated partial thromboplastin time increase than UFH (p<0.01). Platelet count exhibited a comparable small decline in both DS-CRRT and UFH-CRRT (p<0.01). No significant bleeding episodes occurred during DS-CRRT. In-hospital mortality was similar in the 2 cohorts. CONCLUSIONS: DS can be suggested as an anticoagulant for CRRT in patients who develop acute renal failure following major cardiovascular surgery.

Use of drugs for nephrolithiasis.

Renal stone disease often begins by renal colic. In order to manage this event adequately, several goals should be pursued: first, attenuate pain; second, favour progression and spontaneous expulsion of stones; third, prevent from obstructive and infectious complications. All of the aforementioned points pertain to medical management of this disease. Concerning prevention, it is widely agreed that pathogenesis of kidney stones is a consequence of abnormalities in urine environment, leading to a disequilibrium between promoters and inhibitors of crystallization. Therefore, the rationale for therapy is to make urine less conductive to stone formation, by both decreasing state of saturation and increasing inhibitory potential. In only some types of stone-forming salts it is possible to obtain undersaturation with the solid phase. Indeed, uric acid stones can be chemically dissolved by using alkali and allopurinol. To a lesser extent, this also applies to cystine stones, with the use of thiols and alkali. In these subsets, the aforementioned tools are also effective to prevent new stone formation. Much more challenging appears the treatment of calcium containing stones. About 10% of such stones is caused by systemic disorders and, in these cases, the prevention of new stones is successfully accomplished by curing the underlying disease. For instance, parathyroidectomy cures calcium nephrolithiasis in case of hyperparathyroidism. However, the majority of patients with calcium stones are idiopathic stone-formers, in whom metabolic abnormalities often occur, namely, hypercalciuria, hyperoxaluria, hypocitraturia. The correction of these abnormalities by using thiazide diuretics, alkaline citrates, potassium phosphate and bisphosphonates is based on the prevailing metabolic defect. Among the most recent available tools, Oxalobacter Formigenes and probiotics have been proposed to treat primary or secondary hyperoxalurias. In general, the treatment of stone disease reduces its recurrence rate, but only seldom results in stable remission. Anyway, less stones mean reduction of the need for urological procedures and the associated infective or obstructive complications. Of course, medical prevention implies financial efforts, but a careful cost to benefit analysis demonstrates that these are well justified.

Computer program to prescribe acetate-free biofiltration as a continuous renal replacement therapy: theoretical description and in vivo validation.

We describe the theoretical features and in vivo assay of an original computer-based program, which describes Na and HCO3 kinetics with acetate-free biofiltration performed as a continuous veno-venous renal replacement therapy (CVVAFB). In 14 patients, CVVAFB sessions were performed as follows. Machine Hospal Prisma, membrane AN69 0.9 m2, blood circuit Hospal M100 pre Set, dialysate bags of electrolyte solution with basic composition of: Na 139 mEq/L, K 2 mEq/L, Ca 3.0 mEq/L, Mg 2 mEq/L, Cl 146 mEq/L, and glucose 5.5 mmol/L. Predilutional infusion bags of 167 mEq/L of NaHCO3 solution (Hospal Biosol). To guide the prescription of the dialysate (QD) and the infusate (QInf ) flow rates we designed a suitable computer program, which calculated Na and HCO3 kinetics and predicted their plasma profiles at equilibrium. Prescribed flow rates were QB 150 ml/min, QD 1636 +/- 42 ml/hr, Q Inf 639 +/- 74 ml/hr and ultrafiltration (UF) rate 110 +/- 41 ml/hr. During CVVAFB, plasma profiles of HCO3 and Na became stable after 24 hr. With HCO3 , the average predicted and observed plasma levels at equilibrium were 27.1 +/- 1.5 and 27.3 +/- 1.5 mEq/L, respectively (p=ns); with Na, the predicted and observed levels at equilibrium were 140.2 +/- 1.8 and 141.3 +/- 1.7 mEq/L, respectively (p=ns). There was a good correlation between predicted and observed values for both Na (p<0.01, r=0.78) and HCO3 (p<0.01, r=0.87). These results confirmed the reliability of our mathematical model for CVVAFB. A Long-term trial is needed to obtain more information on its clinical effects and compare CVVAFB with other continuous renal replacement therapy techniques.

Crystallization inhibitors in the pathophysiology and treatment of nephrolithiasis.

It is currently agreed that stone formation in the urinary tract requires supersaturation with respect to a given solid phase. However, this principle fully applies only to stones other than calcium-containing stones, in which case compounds acting as inhibitors are postulated to naturally occur in urine. Stone formation would therefore ensue from an imbalance between promoters and inhibitors. The saturation state can be estimated by means of computer model systems based on ab initio calculations, which account for the main soluble complexes formed in urine between relevant cations and anions. This estimates the overall promoting potential of urine. However, in the case of calcium nephrolithiasis, supersaturation does not make a clear-cut separation between normal subjects and patients. Several studies in the last two decades have identified many inhibitors of calcium oxalate and calcium phosphate crystallization, which are classified into the ionic and macromolecular. They have been shown to act on kinetics by interfering with nucleation, growth and aggregation of crystals. Unfortunately, except for citrate, none of the newly discovered substances has been definitely characterized in its molecular composition and structure, type and potency of inhibition, differences in concentration and structure between stone-forming and non stone-forming subjects. Citrate exhibits a dual action in urine, opposing crystal formation by both thermodynamic and kinetic mechanisms. At present it is the only natural inhibitor which can be measured in urine, quantitated as to inhibitory activity and used in medical treatment.

Cost analysis of blood purification in intensive care units: continuous versus intermittent hemodiafiltration.

BACKGROUND: We implemented a program for continuous renal replacement therapies (CRRT) in intensive care units (ICU) based on the cooperative work of dialysis and ICU personnel. Our aim was to report the main details of this program and compare its cost with that of intermittent hemodiafiltration (IHDF). METHODS: The study referred to 181 ICU patients with renal failure. We considered the costs of both technical devices and assisting personnel. CRRT was performed as continuous veno-venous hemodiafiltration (CVVHDF) (24 hr daily); dialysis and ICU nurses shared surveillance. Only dialysis nurses performed IHDF (as acetate-free biofiltration, 4 hr daily) in the ICU. RESULTS: The daily cost of CRRT was Euro 276.70; of which 79% was for devices and 21% was for human resources. Nurse surveillance required 141 min per day, ICU nurses supplied 55% (77 min) and dialysis nurses 45% (64 min). On average, CRRT surveillance required less than 1 min/nurse/hr for both dialysis and ICU nurses. The daily cost of 4-hr IHDF sessions of was Euro 247.83, of which 44% was for technical devices and 56% was for human resources. CONCLUSIONS: The cooperation between dialysis and ICUs improved the use of human resources and allowed us to supply CRRT to all critically ill patients with acute renal failure. The expenditure for CRRT was 12% higher than that for IHDF, due to the cost of technical devices.