Adherence of Renal Transplant Recipients to Once-daily, Prolonged-Release and Twice-daily, Immediate-release Tacrolimus-based Regimens in a Real-life Setting in Sweden.

BACKGROUND: In this study we investigated medication adherence of kidney transplant patients (KTPs) to an immediate-release tacrolimus (IR-T) regimen and, after conversion, to a prolonged-release tacrolimus (PR-T) regimen in routine clinical practice. METHODS: This was a noninterventional, observational, multicenter Swedish study. We included adult KTPs with stable graft function, remaining on IR-T or converting from IR-T to PR-T. Data were collected at baseline, and months 3, 6, and 12 postbaseline. The primary endpoint was adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS). Secondary assessments included tacrolimus dose and trough levels, clinical laboratory parameters (eg, estimated glomerular filtration rate), and adverse drug reactions (ADRs). RESULTS: Overall, 233 KTPs were analyzed (PR-T, n = 175; IR-T, n = 58). Mean change in PR-T dose from baseline (4.8 mg/d) to month 12 was -0.2 mg/d, and for IR-T (4.2 mg/d) was -0.4 mg/d; tacrolimus trough levels remained similar. Overall adherence was similar between baseline and month 12 in both groups (PR-T: 54.4% vs 57.0%, respectively; IR-T: 65.5% vs 69.4%); timing adherence followed a similar pattern. The probability of taking adherence improved between baseline and month 12 (odds ratio, 1.97; P = .0092) in the PR-T group only. Mean BAASIS visual analog scale score at baseline was 94.3 ± 11.1% (PR-T) and 95.3 ± 7.6% (IR-T), and >95% at subsequent visits. Laboratory parameters remained stable. Eight (4.6%) patients receiving PR-T (none receiving IR-T) had ADRs considered probably/possibly treatment-related. CONCLUSION: Disparity existed between high, patient-perceived and low, actual adherence. Overall adherence to the immunosuppressive regimen (measured by BAASIS) did not improve significantly over 12 months in stable KTPs converting to PR-T or remaining on IR-T; renal function remained stable.

Adherence of Renal Transplant Recipients to Once-daily, Prolonged-Release and Twice-daily, Immediate-release Tacrolimus-based Regimens in a Real-life Setting in Sweden.

BACKGROUND: In this study we investigated medication adherence of kidney transplant patients (KTPs) to an immediate-release tacrolimus (IR-T) regimen and, after conversion, to a prolonged-release tacrolimus (PR-T) regimen in routine clinical practice. METHODS: This was a non-interventional, observational, multicenter Swedish study. We included adult KTPs with stable graft function, remaining on IR-T or converting from IR-T to PR-T. Data were collected at baseline, and months 3, 6, and 12 post-baseline. The primary endpoint was adherence using the Basel Assessment of Adherence to Immunosuppressive Medication Scale (BAASIS©). Secondary assessments included tacrolimus dose and trough levels, clinical laboratory parameters (eg, estimated glomerular filtration rate), and adverse drug reactions (ADRs). RESULTS: Overall, data from 233 KTPs were analyzed (PR-T, n = 175; IR-T, n = 58). Mean change in PR-T dose from baseline (4.8 mg/d) to month 12 was -0.2 mg/d, and for IR-T (4.2 mg/d) was -0.4 mg/d; tacrolimus trough levels remained similar. Overall adherence was similar between baseline and month 12 in both groups (PR-T: 54.4% vs 57.0%, respectively; IR-T: 65.5% vs 69.4%); timing adherence followed a similar pattern. The probability of taking adherence improved between baseline and month 12 (odds ratio, 1.97; P = .0092) in the PR-T group only. Mean BAASIS visual analog scale score at baseline was 94.3 ± 11.1% (PR-T) and 95.3 ± 7.6% (IR-T), and >95% at subsequent visits. Laboratory parameters remained stable. Eight (4.6%) patients receiving PR-T (none receiving IR-T) had ADRs considered probably/possibly treatment-related. CONCLUSION: Disparity existed between high, patient-perceived and low, actual adherence. Overall adherence to the immunosuppressive regimen (measured by BAASIS) did not improve significantly over 12 months in stable KTPs converting to PR-T or remaining on IR-T; renal function remained stable.

Single or double arteries in the remnant kidney after donation: influence on the long-term outcome of the donor.

BACKGROUND: A kidney with a single artery is preferred for donation. We wondered how often the donor is left with double or triple arteries, and whether this has any implications for long-term kidney function. METHODS: The consecutive living donors from 1984 to 1988 were reevaluated for kidney function and outcome. RESULTS: In total, 154 donor nephrectomies were performed with an open anterior technique. Ninety-eight patients were left with a single artery to the remnant kidney and 56 (36%) with more than one. Six individuals were left with 3 arteries. The mean age at donation was 48 +/- 12 years and mean age at reevaluation was 68 +/- SD 12 years. In the group with a remnant single artery, the mean preoperative serum creatinine level was 87 +/- 11 micromol/L, at 6 months it was 127 +/- 20 micromol/L, and in 2007 it was 90 +/- SD 23 micromol/L. The estimated glomerular filtration rate (GFR) was 67 +/- 18 mL/min. Thirty-three percent of donors (19/58) had developed hypertension. Among the group with multiple remnant arteries, the mean preoperative serum creatinine level was 87 +/- SD 11 micromol/L, at 6 months it was 131 +/- 21 micromol/L, and in 2007 it was 100 +/- 45 micromol/L. Estimated GFR was 64 +/- 16) mL/min. Twenty-eight percent of the donors (10/36) had developed hypertension. CONCLUSIONS: One third of kidney donors were left with double or triple arteries to the remnant kidney. The 20-year follow-up showed no significant difference in the renal function between the 2 groups.

Acute renal failure after a holiday in the tropics.

A 20-year-old, previously healthy woman, presented with high fever, headache and myalgia 3 days after her return from a holiday in Southeast Asia. Laboratory data on admission demonstrated a pronounced increase in plasma creatinine, marked thrombocytopenia and moderately elevated liver aminotransferases. After having ruled out malaria, dengue fever was primarily suspected and supportive intravenous fluid therapy was initiated. Still, 1 day after admission, platelet counts dropped even further and she became anuric although she did not appear hypovolemic. On day 2 after admission, urine production commenced spontaneously and the patient slowly recovered. All laboratory test results had returned to normal approximately 2 months later. Serological analysis for dengue fever was negative. It turned out that the patient had been trekking in the jungle while in Thailand and we, therefore, analyzed serology for Leptospira spirochetes which was clearly positive. The patient was diagnosed with leptospirosis which is a serious condition associated with a high mortality when complicated by acute renal failure. Differential diagnoses in patients with acute renal failure and tropical infections are reviewed. The importance of early recognition of leptospirosis, and prompt treatment with antibiotics in suspected cases, is emphasized.

Renal transplantation after Cortinarius speciosissimus poisoning.

During the years 1979-1993 22 individuals were intoxicated in Sweden by the mushroom Cortinarius speciosissimus. Nine of them developed end-stage renal failure (ESRF), and we describe five who have received renal transplants. Three were transplanted after 6-9 months on haemodialysis; the other two regained some renal function after 2-6 months on haemodialysis, but had to be restarted on dialysis 24-30 months later and were eventually transplanted. Two patients had kidneys donated by a father and a brother respectively, three had cadaveric organs. All five developed satisfactory renal function with current glomerular filtration rate (GFR) 31-79 ml/min (mean 56.2) after 5-10 (mean 7.0) years. To our knowledge, renal transplantation after Cortinarius poisoning has not been reported before.

Interferon gamma inhibits the intracellular multiplication of Neospora caninum, as shown by incorporation of 3H uracil.

An assay was developed to quantify the growth of two different isolates of the protozoon Neospora caninum within ovine fibroblast cells in vitro by differential uptake of 3H uracil. The NC-1 isolate of N. caninum multiplied more quickly in culture than the NC Liverpool isolate, as reflected by increased incorporation of isotope by the former over a shorter period of time. After the parasites had left the ruptured host cells, there was very little incorporation of isotope. This suggested that multiplication occurred within and not outside the cells. Treatment of the cells with ovine recombinant interferon gamma for 24 h before infection significantly inhibited intracellular multiplication of the parasite.

Neospora caninum in dogs: detection of antibodies by ELISA using an iscom antigen.

An indirect enzyme linked immunsorbent assay (ELISA) for detection of antibodies to Neospora caninum in serum from dogs is described. Extracted tachyzoite proteins incorporated into immunostimulating complexes (iscoms) were used as coating antigen. A mixture of a monoclonal antibody to dog immunoglobulin G and a horse radish peroxidase conjugated antibody to mouse Ig was used to detect bound antibody. When the iscom preparation was analysed by means of sodium dodecyl sulphate polyacrylamide gel electrophoresis it appeared to consist of a restricted number of proteins compared with whole parasite homogenates. In immunoblot analysis, using N. caninum positive sera from rabbits and dogs as probes, the major antigens recognized had approximate molecular weights between 30 and 45 and 17 to 19 kDa. Compared with an ELISA using a crude solubilized tachyzoite antigen, the iscom ELISA substantially improved the sensitivity and specificity (to 97.6% and 95.6%, respectively, against an immunofluorescence test, IFAT, as indicator of true status). There was a statistically significant positive correlation between IFAT titres and iscom ELISA OD450 values. The iscom ELISA absorbances (and the IFAT titres) of dogs with proven clinical infections were not higher than those from nonclinically affected, putatively infected dogs.

Isolation and nephrotoxic studies of orellanine from the mushroom Cortinarius speciosissimus.

A nephrotoxic substance has been isolated from Cortinarius speciosissimus. The 1H-NMR and 13C-NMR mass spectra indicated the chemical structure to be 3,3',4,4'-tetrahydroxy-2,2'-bipyridine-N-N'-dioxide. The toxin was quantitated using reversed phase high performance liquid chromatography (HPLC) with electrochemical detection. The detection limit of this method was 500 pg, corresponding to a signal-to-noise ratio of 2.5. The toxin had an LD50 in mice of approximately 20 mg/kg i.p. Light microscopic examination of the kidneys of mice surviving treatment with the toxin showed interstitial nephritis and tubular necrosis.

Acute renal failure after intoxication with Cortinarius mushrooms.

Four previously healthy young adults developed the clinically recognised features of Cortinarius poisoning 3-4 days after intoxication. Two patients treated with haemoperfusion and haemodialysis 5 days after ingestion of the mushrooms regained normal kidney function. Two patients treated late with single haemoperfusion or dialysis had irreversible renal failure. The clinical results and our experimental studies on the toxic principle of the mushrooms indicate that early treatment with HP and HD may be important in order to avoid the development of irreversible renal failure.