Secondary Immunosuppression in Pediatric Kidney Transplant Recipients.

OBJECTIVES: Currentimmunosuppressive treatments for kidney transplant recipients have improved graft viability at the expense of impaired immune surveillance. The tools for monitoring immune status in pediatric kidney transplant recipients have not been widely investigated. Better knowledge could help recognize over immunosuppression and allow implementation of individualized preventive strategies. MATERIALS AND METHODS: This retrospective and observational study included 28 pediatric kidney transplant recipients treated at a tertiary hospital. We measured peripheral blood lymphocyte subpopulations, immunoglobulins, immunosuppressivedrug levels, and viral loads. Reference analytical values for different age ranges were used to determine immune status. We recorded overall hospitalizations due to opportunistic infections and positive viral loads posttransplant. RESULTS: We found hypogammaglobulinemia and lymphopenia in 19% and 41% of the patients, respectively. Peripheral blood lymphocyte subpopulations were below normal limits in one-third of the sample. These parameters were not related to the current number or plasma levels of immunosuppressive drugs. During follow-up, cytomegalovirus, Epstein-Barr virus, and BK virus viremias were detected in 60.7% of the patients. Admissions due to opportunistic infections happened in 57.1%, mainly related to severe viral disease (30%) or gastrointestinal infections (26.7%). Most occurred in younger transplant recipients and during the first 2 years posttransplant (73.3%). We found no significant relation between peripheral blood lymphocyte subpopulations and hospital admissions for opportunistic infections or positive viral loads during follow-up. CONCLUSIONS: Recurrent hospitalizations for opportunistic infections and analytical disorders in the immune system suggested that secondary immunosuppression in pediatric kidney transplant recipients was frequent. Immunosuppression was not directly related to plasma drug levels or the number of immunosuppressive drugs. Thus, immune monitoring might be helpful in combination with immunosuppressant levels to assess immunosuppression status and to establish individualized preventive measures.

Kidney function in patients with primary distal renal tubular acidosis.

BACKGROUND: Recent reports indicate that chronic reduction of glomerular filtration rate (GFR) is common in patients with distal renal tubular acidosis (DRTA). Factors responsible for decreased GFR need clarification. METHODS: We reviewed records of 25 patients with genetically confirmed DRTA included in the RenalTube database. Patients < 18 years at diagnosis and having at least one annual follow-up were selected and classified in two groups according to GFR ≥ 90 (normal GFR) or < 90 mL/min/1.73 m2 (low GFR) after median follow-up of 8.8 years. RESULTS: Eighteen and seven patients had normal and low GFR (X ± SEM, 121.16 ± 28.87 and 71.80 ± 10.60 mL/min/1.73 m2, respectively, p < 0.01). At diagnosis, these 2 subgroups did not differ in sex, age, underlying mutated gene, GFR, height SDS, or percentage of ultrasound nephrocalcinosis. Serum creatinine (SCr) was different but likely due to median ages of presentation being 0.6 and 4.0 in normal and low GFR patients, respectively. On the last recorded visit, no differences between both groups were found in serum bicarbonate, serum potassium, or alkali dosage. Height SDS of patients with normal GFR was - 0.15 ± 0.47 whereas it was - 1.06 ± 0.60 in the low GFR group (p = 0.27). Interestingly, 23% of the whole group had low birth weight (LBW; < 2500 g), equating to 20% and 29% in the normal and low GFR patients, respectively (p = 0.65). CONCLUSIONS: Our findings confirm the risk of kidney function reduction in patients with DRTA of pediatric age onset, suggesting that low GFR is related with less favorable growth outcome and discloses the high frequency of LBW in primary DRTA, a hitherto unrecognized feature.

Incomplete distal renal tubular acidosis in children.

AIM: To describe incomplete distal renal tubular acidosis (iDRTA) in paediatric patients, a term used for the diagnosis of patients who do not develop spontaneous overt metabolic acidosis but are unable to acidify the urine in response to an ammonium chloride load. METHODS: Tests used to explore urinary acidification were revised. In addition, publications in English extracted from 161 entries yielded by a PubMed database search, using 'incomplete distal renal tubular acidosis' as keyword, were reviewed. RESULTS: Incomplete distal renal tubular acidosis has mostly been identified in adults with autoimmune diseases, nephrolithiasis, nephrocalcinosis and/or osteopenia. iDRTA has been reported in few paediatric patients with rickets, congenital abnormalities of kidney and urological tract and/or growth failure. The pathophysiological mechanisms potentially responsible for the defect of urinary acidification are discussed as well as the clinical and biochemical findings of iDRTA described in children. CONCLUSION: The presentation of iDRTA in children differs from adults. The clinical and biochemical features of iDRTA are not well characterised in paediatric patients. The detection of iDRTA in groups of population such as heterozygous carriers of primary DRTA gene mutations and children with hypocitraturia or hypercalciuria might be of clinical interest to better know the pathophysiology and natural history of iDRTA.

Distal renal tubular acidosis. Clinical manifestations in patients with different underlying gene mutations.

BACKGROUND: To evaluate whether there are differences in the phenotype of primary distal renal tubular acidosis (dRTA) patients according to the causal defective gene. METHODS: Twenty-seven non-oriental patients with genetically confirmed dRTA were grouped according to the identified underlying mutations in either ATP6V1B1 (n = 10), ATP6V0A4 (n = 12), or SLC4A1 (n = 5) gene. Demographic features, growth impairment, biochemical variables and presence of deafness, nephrocalcinosis, and urolithiasis at diagnosis were compared among the three groups. RESULTS: Patients with SLC4A1 mutations presented later than those with ATP6V1B1 or ATP6V0A4 defects (120 vs. 7 and 3 months, respectively). Hearing loss at diagnosis was present in the majority of patients with ATP6V1B1 mutations, in two patients with ATP6V0A4 mutations, and in none of cases harboring SLC4A1 mutations. Serum potassium concentration (X ± SD) was higher in SLC4A1 group (3.66 ± 0.44 mEq/L) than in ATP6V0A4 group (2.96 ± 0.63 mEq/L) (p = 0.046). There were no differences in the other clinical or biochemical variables analyzed in the three groups. CONCLUSIONS: This study indicates that non-oriental patients with dRTA caused by mutations in the SLC4A1 gene present later and have normokalemia or milder hypokalemia. Hypoacusia at diagnosis is characteristically associated with ATP6V1B1 gene mutations although it may also be present in infants with ATP6V0A4 defects. Other phenotypical manifestations do not allow predicting the involved gene.