Different modes of renal proximal tubule regeneration in health and disease

Tissues are equipped with reasonable strategies for repair and regeneration and the renal proximal tubule(PT) is no exception. New information has become available on the mode of PT regeneration in mammals. Unlike the intestinal epithelium with a high rate of turnover maintained by the stem cell system, the kidney has low turnover under normal physiological conditions. The PT seems to be maintained physiologically by hyperplasia, a regenerating system with self-renewal of mature tubular cells. This mode of regeneration is advantageous for effective replenishment of randomly isolated and eliminated tubular cells by self-renewal of adjacent cells. On the other hand, it has been suggested that dedifferentiation of mature tubular cells plays a role in regeneration after acute kidney injury. Recent studies employing genetic labeling and DNA-labeling techniques have confirmed that the proliferation of preexisting injured mature tubular cells contributes mainly to PT regeneration in ischemic reperfusion injury. This mode of regeneration is beneficial with regard to the rapid reparation of focally injured tubules often induced by ischemic reperfusion injury. What happens, however, when the PT is homogeneously injured with almost no remaining surviving cells? Is the PT equipped with another backup regeneration system, e.g., the stem cell system? Is it possible that certain types of renal injuries evoke a stem cell response whereas others do not? This review focuses on all three possible modes of tissue regeneration(compensatory hyperplasia, dedifferentiation and stem cell system) in mammals and their involvement in PT regeneration in health and disease.

Case of human immunodeficiency virus infection presenting as a tip variant of focal segmental glomerulosclerosis: A case report and review of the literature

The incidence of the collapsing variant of focal segmental glomerulosclerosis(FSGS) as a human immunodeficiency virus(HIV)-associated nephropathy has reduced since the introduction of antiretroviral therapy(ART). However, the incidence of other variants of FSGS, except for the collapsing variant, is increasing, and its therapeutic strategies remain uncertain. A 60-year-old HIV infected man in remission with ART was admitted for progressive renal insufficiency and nephrotic-ranged proteinuria. Renal biopsy revealed a tip variant of FSGS and his clinical manifestations resolved with corticosteroid therapy. HIV infected patients might develop non-collapsing FSGS, including tip variant of FSGS and corticosteroid therapy might be effective for them. A renal biopsy might be essential to determine the renal histology and to decide on corticosteroid therapy.

Calcitriol-induced hypercalcemia in a patient with granulomatous mycosis fungoides and end-stage renal disease

An 86-year-old man, diagnosed as having mycosis fungoides in May 2008 and treated with repeated radiation therapy, was admitted to our hospital for initiation of hemodialysis due to end-stage renal disease(ESRD) in April 2012. On admission, his corrected serum calcium level was 9.3 mg/d L, and his intact parathyroid hormone level was 121.9 pg/mL(normal range 13.9-78.5pg/mL), indicating secondary hyperparathyroidism due to ESRD. After starting hemodialysis, urinary volume diminished rapidly. The serum calcium level increased(12.7 mg/dL), and the intact parathyroid hormone level was suppressed(< 5 pg/m L), while the 1,25-dihy-droxyvitamin D3(calcitriol) level increased(114 pg/mL, normal range: 20.0-60.0 pg/m L) in June 2012. The possibilities of sarcoidosis and tuberculosis were ruled out. Skin biopsies from tumorous lesions revealed a diagnosis of granulomatous mycosis fungoides. The serum soluble interleukin-2 receptor levels and the degrees of skin lesions went in parallel with the increased serum calcium and calcitriol levels. Therefore, the patient was diagnosed as having calcitriol-induced hypercalcemia possibly associated with granulomatous mycosis fungoides. Granulomatous mycosis fungoides is rare, and its association with calcitriol-induced hypercalcemia has not been reported. Careful attention to calcium metabolism is needed in patients with granulomatous mycosis fungoides, especially in patients with ESRD.