Patient mortality after graft failure reduces kidney transplant patient survival only in the long term: an "intention to treat" analysis.

The benefits of kidney transplantation over dialysis on patient survival have been demonstrated without considering the outcomes of patients with graft loss. To determine whether mortality after graft failure reduced the transplantation advantage in patient survival, we retrospectively reviewed the outcomes of 918 first-deceased renal transplant recipients from May 1979 to August 2005. Patient survivals were 88% and 72% at 10 and 20 years; cancer (26%) and cardiovascular disease (25%) were the major causes of death. Graft survivals were 72% and 50% at 10 and 20 years; chronic rejection was the major cause of graft loss (50%). Patient outcomes after return to dialysis were reviewed in 224 of 240 patients. The survivals were 97%, 83%, and 70% at 1, 5, and 10 years, respectively; cardio-cerebrovascular disease (56%), infections (9%), cachexia (9%), and cancer (8%) were the major causes of death. Mortality correlated with patient age at transplantation (P< .001). Re-listed patients (96 of 224) were younger (32+/-10 vs 43+/-11 years; P< .001), had a shorter dialysis period pretransplant (3.2+/-3.1 vs 4.3+/-3.9 years; P< .03), and a better survival at 10 years (98% vs 56%; P< .001). Ten-year mortality for patients who returned to dialysis was 20% higher than for patients with a functioning graft (P< .001). The reduction in overall patient survival was 2.2% at 10 years (P=NS), 5% at 15 years (P=NS), and 14% at 20 years (P< .05). The same results have been demonstrated for patients >50 years at transplantation. In conclusion, the mortality rate after return to dialysis did not influence the long-term benefits of kidney transplantation.

[Successful treatment with liposomal doxorubicin and foscarnet in a patient with widespread Kaposi's sarcoma and human herpes virus 8-related, serious hemophagocytic syndrome, after renal transplantation]. / Efficacia del trattamento con doxorubicina liposomiale e foscarnet in un caso di sarcoma di Kaposi disseminato e grave sindrome emofagocitica herpes virus 8 correlate, nel post-trapianto di rene.

BACKGROUND: It is well known that the human herpes virus 8 (HHV8) is linked to several malignancies such as Kaposi's sarcoma (KS). Moreover, pancytopenia due to hemophagocytic syndrome could be associated with HHV8 infection. In renal transplant recipients affected by KS, the tapering of immunosuppression often leads to KS remission, but also results in graft loss in >50% of cases. Chemotherapy and antiviral therapy have also been used, mainly in the presence of visceral involvement. CASE REPORT: We describe a transplant recipient with widespread cutaneous and visceral KS HHV8 associated, complicated by hemophagocytic syndrome. At transplantation the patient's serology for HHV8 was negative, but thereafter it became positive. The first step in treatment (cyclosporine dose reduction until suspension) failed to improve the clinical course. Therefore, therapy combining liposomal doxorubicin and foscarnet was started. Clearance of HHV8 in the blood and complete resolution of the KS lesions were achieved. Immunosuppression with cyclosporine was resumed. No KS relapse has occurred, blood tests for HHV8 are negative, and graft function is good after a 5-yr follow-up. CONCLUSIONS: Therapy combining liposomal doxorubicin and foscarnet was effective in this renal transplant recipient with KS and HHV8 infection and enabled us to resume immunosuppressive therapy; therefore, reducing the risk of acute/chronic rejection.

Experience with cyclosporine.

Six hundred thirty-eight cadaveric kidney transplant patients between 1983 and 2001 were treated with cyclosporine (CsA) for 87 +/- 58 months. Among 571 patients with follow-up greater than 12 months, the 15-year renal function was investigated to assess the probability of a >30% increase in serum creatinine (sCr) above the month-6 value (baseline) and the impact on graft survival. At 15 years, patient and graft survival rates were 82.7% and 56.1%, respectively, with a 19.5-year half-life (censored for deaths). The main causes of graft loss were chronic rejection (33.0%) and patient death (24%). Cardiovascular disease and neoplasms were the main causes of death. Renal function remained stable in 266 patients (46.6%) with excellent sCr values observed even after a 15-year treatment period. An increased sCr was observed in 305 patients (53.4%) with a 15-year probability of 74%. In 178 patients (59.3%) it was self-limited; their grafts are still functioning well. One hundred three patients (32.8%) lost their graft which was more likely when the sCr had increased >45%. Twenty-four patients (7.9%) died with a functioning graft. Multivariate analysis showed the progression of graft deterioration to be related to proteinuria (P<.0001), a late acute rejection episode (P<.002), or the extent of sCr increase (P<.008). In conclusion, the long-term use of CsA has allowed us to achieve excellent long-term patient and transplant survival rates. Our data indicate a high 15-year probability of an increased sCr, but the rate of progression is slow.

[Cancer after kidney transplantation]. / La complicanza neoplastica dopo trapianto di rene.

In our experience, cancer is the second cause of death after renal transplantation. In fact, 27% of the deaths we observed at 15-year follow-up were due to neoplasm and 30% to cardiovascular disease. Cancer is a late complication that becomes more common after the fifth year of transplantation. The probability of suffering from cancer is 8.2% and 29.2% at 5 and 15 year, respectively. More specifically, after a 15-year follow-up, the probability rate for skin cancer is 16.4%, solid cancer 12.8%, lymphoproliferative disease (PTLD) 3% and Kaposi's sarcoma 2.2%, respectively. PTLD has the highest mortality rate (44% after 12 months from diagnosis), followed by solid cancer (24%) and Kaposi's sarcoma (8%). According to the literature, patient-age is the main risk factor for neoplasm; double therapy (Cyclosporine + Azathioprine) can increase both the skin cancer and PTLD risk but not the risk of solid cancer. No difference between Cyclosporine and Tacrolimus has been observed in the incidence of neoplasm. Both in vitro and in vivo studies have documented the ability of Rapamycin to inhibit primary and metastatic tumour growth. If these results are also obtained on patients, Rapamycin will be of considerable interest for the future of immunosuppression. In cancer patients, immunosuppression must always be reduced, especially when dealing with PTLD. After standard chemotherapy, patient mortality rate due to infectious complications is very high. Therefore, chemotherapy should be a second-choice therapy and administered in reduced doses. Many studies have documented that lymphocytes B-cells CD20 positive PTLD can be efficiently treated with Retuximab.

Clinical and morphological features of kidney involvement in primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome is a connective tissue disorder affecting primarily the lacrimal and salivary glands, resulting in xerophtalmia and xerostomia. Extraglandular manifestations are frequent and may include renal involvement. METHODS: We studied the prevalence and nature of kidney involvement in 60 Italian patients with primary Sjögren's syndrome, diagnosed according to the European classification criteria. The following renal laboratory tests were performed in all patients: electrolytes in serum and in 24-h urine, creatinine in serum and in 24-h urine, venous pH and HCO(3)(-), urinalysis, urine culture, urinary osmolality and urine pH. A water deprivation test was performed in patients with morning urine osmolalities below the reference values adjusted for age. An oral ammonium chloride loading test was performed in patients with urine pH above 5.5 from morning samples. Renal biopsy was performed in patients with renal involvement. RESULTS: Sixteen patients (27%) had laboratory evidence of tubular and/or glomerular dysfunction. A variable degree of creatinine clearance reduction was found in eight patients (13%); frank distal tubular acidosis in three (5%); hypokalaemia in four (7%); and pathological proteinuria in 12 (20%). Urine concentrating capacity was defective in 10 out of 48 (21%) tested patients. Only four patients presented with overt clinical manifestations, including hypokalaemic tetraparesis (1), nephrotic syndrome (2), recurrent renal stones with flank pain and haematuria (1). In two patients, signs of renal involvement preceded the onset of sicca syndrome. Renal biopsies from nine patients showed tubulo-interstitial nephritis in six and glomerular disease in three. Patients with renal involvement had a significantly shorter disease duration compared with patients without renal abnormalities. CONCLUSIONS: Kidney involvement is a frequent extraglandular manifestation of primary Sjögren's syndrome. It is rarely overt and may precede the onset of subjective sicca syndrome.

Autosomal dominant medullary cystic disease: a disorder with variable clinical pictures and exclusion of linkage with the NPH1 locus.

BACKGROUND: The nephronophthisis-medullary cystic disease (NPH/MCD) complex represents a heterogeneous group of hereditary tubulointerstitial nephritis. The most common variant is juvenile recessive NPH, for which a gene locus (NPH1) has been mapped on chromosome 2q13. MCD is a less common dominant condition usually recognized later in life, which resembles NPH in many aspects, still presenting remarkable clinical differences. Nothing is known about the chromosome locus of MCD. METHODS: Five MCD families were studied. Diagnosis was made by inference from family history, type of inheritance, clinical signs and histology. Multipoint linkage analysis was performed by markers D2S293, D2S340 and D2S160 spanning the entire NPH1 locus. RESULTS: Diagnosis of MCD was made in 28 affected members (16 males; 12 females), belonging to five families. Histological diagnosis was available in 10 patients; clinical diagnosis in 11; seven deceased relatives had diagnosis of chronic nephritis. The age at diagnosis ranged from 8 to 65 years. Renal medullary cysts were found in a minority of patients. In family 1, the disease was associated with hyperuricaemia and gouty arthritis. Progression of renal disease presented intra- and extra-family variability with members of the same family showing mild elevation of creatinine or terminal renal failure. The NPH1 locus associated to recessive NPH was excluded from linkage to the dominant MCD. CONCLUSIONS: MCD might be more common than previously assumed. Variability in clinical presentation and absence of histopathological hallmarks contribute to make the diagnosis uncommon. The most remarkable clinical difference with NPH is the age of onset in some kindreds and a delayed progression towards renal failure. The exclusion of linkage to the NPH1 locus suggests the existence of an MCD responsible locus, still to be mapped.

Evidence for an independent role of metabolic acidosis on nutritional status in haemodialysis patients.

BACKGROUND: Malnutrition in haemodialysis (HD) patients has been referred to underdialysis with low protein intake, and to acidosis. However, the separate effects of underdialysis and acidosis on nutrition have not been clearly demonstrated. To evaluate the role of the dialysis dose and of metabolic acidosis on nutrition, we measured the predialysis serum HCO3, pH, serum albumin, PCRn, Kt/V, and BMI in 81 uraemic patients on maintenance bicarbonate HD for 93+/-80 months. Patients with chronic liver diseases, malignancies, and cachexia were excluded. RESULTS: Mean age was 59+/-17 years, Kt/V was 1.29+/-0.21, PCRn 1.06+/-0.22 g/kg/day, serum albumin 4.07+/-0.28 g/dl, BMI 23+/-4 kg/m2, HCO3 21.1+/-1.9 mmol/l, pH 7.36+/-0.04. Serum albumin showed a significant direct correlation with: PCRn (P=0.001), HCO3 (P=0.001), pH (P=0.002), but no correlation with Kt/V and BMI. Serum HCO3 correlated inversely with PCRn (P=0.027). Multiple regression analysis confirmed the significant role of serum bicarbonate and age, but not of Kt/V, on serum albumin concentrations. The role of PCRn appeared to be marginal compared to serum bicarbonate in determining serum albumin levels. Dividing patients into two groups, serum albumin was 3.96+/-0.22 g/dl with HCO3 < or = 20 mmol/l and 4.18+/-0.31 g/dl in those with serum HCO3 > or = 23 mmol/l (P=0.002). PCRn in the same groups was respectively 1.14+/-0.24 g/kg/day and 1.01+/-0.23 g/kg/day (P=0.03). Most importantly, serum albumin levels did not appear to be affected by the dialysis dose, with Kt/V ranging from 0.90 to 1.88. CONCLUSIONS: In HD patients with adequate Kt/V, metabolic acidosis exerts a detrimental effect on serum albumin concentrations partially independently of the protein intake, as evaluated by PCRn. In the presence of moderate to severe metabolic acidosis, PCRn does not reflect the real dietary protein intake of the patients, probably as a result of increased catabolism of endogenous proteins. For this reason PCRn should be considered with caution as an estimate of the dietary protein intake in HD patients in the presence of metabolic acidosis.

Blood volume changes during three different profiles of dialysate sodium variation with similar intradialytic sodium balances in chronic hemodialyzed patients.

The aim of this study was to evaluate the effects on blood volume (BV) preservation of three different profiles of dialysate sodium variation with similar intradialytic sodium balances. Ten uremic patients aged 50 +/- 11 years receiving regular bicarbonate hemodialysis for 49 +/- 57 months were studied. Each patient underwent three hemodialysis treatments with different modalities of dialysate sodium profiles: constant sodium hemodialysis (CHD), high-low sodium hemodialysis (H-LHD), and low-high sodium hemodialysis (L-HHD). In CHD, the dialysate sodium concentration was 141 mEq/L and did not change during treatment. In H-LHD and L-HHD, the dialysate sodium concentration at the start of dialysis was 160 mEq/L and 133 mEq/L, respectively, and remained constant for 60 minutes. At this time, a single-step break point of variation of dialysate sodium concentration occurred. The dialysate sodium concentration changed according to a model aimed to keep identical the amount of dialysate sodium exchanged in the three different dialysis procedures. The duration of hemodialysis, the blood flow rate, the dialysate flow rate, and the dialysis membrane were the same for all three different hemodialysis modalities. The ultrafiltration rate was kept constant during treatment. Total dialysate collection and intradialytic sodium balance were calculated for each hemodialysis session. Blood pressure and heart rate were monitored at 10-minute intervals; percent reductions of BV (%R-BV) were continuously monitored by an online optical reflection method (Hemoscan; Hospal-Dasco, Medolla, Italy). The results have shown a lower intradialytic %R-BV with H-LHD compared with L-HHD and CHD. No differences in total ultrafiltration rate, systolic and diastolic blood pressures, and heart rate were observed among the three different dialysis procedures. The total dialysate sodium collected and the intradialytic sodium balances were very similar among the three different dialysis procedures, confirming the accuracy of the precision of the sodium model used. The H-LHD sodium profile may be a useful tool in the prevention of excessive %R-BV and of dialysis intolerance episodes.