Tubular Epithelial Regeneration Research Articles

Pharmacological induction of hypoxia-inducible transcription factor ARNT attenuates chronic kidney failure.

Progression of chronic kidney disease associated with progressive fibrosis and impaired tubular epithelial regeneration is still an unmet biomedical challenge because, once chronic lesions have manifested, no effective therapies are available as of yet for clinical use. Prompted by various studies across multiple organs demonstrating that preconditioning regimens to induce endogenous regenerative mechanisms protect various organs from later incurring acute injuries, we here aimed to gain insights into the molecular mechanisms underlying successful protection and to explore whether such pathways could be utilized to inhibit progression of chronic organ injury. We identified a protective mechanism controlled by the transcription factor ARNT that effectively inhibits progression of chronic kidney injury by transcriptional induction of ALK3, the principal mediator of antifibrotic and proregenerative bone morphogenetic protein-signaling (BMP-signaling) responses. We further report that ARNT expression itself is controlled by the FKBP12/YY1 transcriptional repressor complex and that disruption of such FKBP12/YY1 complexes by picomolar FK506 at subimmunosuppressive doses increases ARNT expression, subsequently leading to homodimeric ARNT-induced ALK3 transcription. Direct targeting of FKBP12/YY1 with in vivo morpholino approaches or small molecule inhibitors, including GPI-1046, was equally effective for inducing ARNT expression, with subsequent activation of ALK3-dependent canonical BMP-signaling responses and attenuated chronic organ failure in models of chronic kidney disease, and also cardiac and liver injuries. In summary, we report an organ-protective mechanism that can be pharmacologically modulated by immunophilin ligands FK506 and GPI-1046 or therapeutically targeted by in vivo morpholino approaches.

Uremic encephalopathy in a rhesus macaque (Macaca mulatta): A case report and a brief review of the veterinary literature.

Uremic encephalopathy is uncommon yet is one of the most severe complications of renal failure. We present a case of acute renal failure and associated cerebral and vascular lesions consistent with uremic encephalopathy in a rhesus macaque (Macaca mulatta). A 14-year-old, female, specific-pathogen-free rhesus macaque presented in lateral recumbency, obtunded, severely dehydrated, and hypothermic, with severe azotemia, mild hyponatremia, hypokalemia, hypochloremia, increased anion gap, and hypercholesterolemia. Due to poor prognosis, the animal was euthanized and a complete necropsy was conducted. The animal had diffuse proximal renal tubular epithelial necrosis and loss; regeneration of tubular epithelium was not observed. There was bilateral necrosis and loss of neurons and glial cells in the hippocampus and deep cerebral cortex with edema and multifocal areas of hemorrhage. We present the first reported case of uremic encephalopathy in a rhesus macaque and describe the associated cerebral and vascular lesions.

Carvacrol attenuates histopathogic and functional impairments induced by bilateral renal ischemia/reperfusion in rats

BackgroundRenal ischemia/reperfusion injury is the most common cause of acute kidney injury, which frequent occurrence in critically ill patients. ObjectivesThe aim of this study was to investigate the role of Carvacrol (CARV) against bilateral ischemia reperfusion (I/R) in rats. MethodsRenal I/R injury were induced by clamping of the left and right renal arteries for 45 min followed by 24 h of reperfusion. Thirty male Sprague–Dawley rats were randomly allocated to three groups (n = 10): the sham-control group, the renal I/R-untreated (I/R-untreated) group, and the I/R-CARV-treated group. At 2 h before reperfusion, the rats in the I/R- CARV -treated group rats received an i.p. injection of 75 mg/kg CARV. Renal function and histological changes were compared and the relevant parameters of oxidative stress and inflammation were detected. ResultsCompared to the sham-control group, I/R led to renal dysfunction as evidenced by higher plasma urea and creatinine along with increase in oxidative stress and histological changes in renal tissues. Treatment with CARV decreased urea, creatinine, and renal MDA and MPO levels, and increased SOD, CAT, GSH activity and eNOS expression in the kidney. In the I/R-CARV-treated group, minimal hydropic changes in the tubular epithelial cells and regeneration of tubular epithelium were observed. ConclusionThese results suggest that CARV treatment could reduce renal injury induced by bilateral renal I/R via anti-inflammatory, antioxidant and cytoprotective effects.

Therapeutic effects of human umbilical cord-derived mesenchymal stem cells against acute tubular necrosis quantified through measures of iNOS, BMP-7 and Bcl-2

Introduction: Acute tubular necrosis (ATN) is the most prevalent cause of acute renal failure (ARF). Mesenchymal stem cell transplantation has been studied as a potential treatment for renal dysfunction due to ATN. Inducible nitric oxide synthase (iNOS), bone morphogenetic protein-7 (BMP-7) and B-cell lymphoma 2 (Bcl-2) are surrogate markers of renal tubular epithelial regeneration and subsequent recovery of renal function following ATN. Methods: Serum creatinine (Scr) and blood urea nitrogen (BUN), as well as expression of iNOS, BMP-7 and Bcl-2 in gentamycin-induced ATN rat kidneys was investigated after human umbilical cord-derived mesenchymal stem cell (HUC-MSC) transplantation. Immunohistochemical staining was performed in 3 groups of rats: gentamycin-induced ATN treated with HUC-MSC, gentamycin-induced ATN without HUC-MSC, and untreated rats not receiving any treatments. Results: HUC-MSC transplantation led to a reduction in Scr and BUN in the kidneys of rats with gentamycin-induced ATN. Expression of iNOS in the HUC-MSC treated group occurred later and the expression levels were much lower during gentamycin-induced ATN compared to rats with ATN that were not treated with HUC-MSC. The expression of BMP-7 and Bcl-2 in the MSC-transplanted group was significantly increased compared to both control groups of rats with injured and healthy renal tubules. Conclusions: HUC-MSCs induce renal protection in a rat model of gentamycin-induced ATN, which is associated with reduced iNOS expression and up-regulation of Bcl-2 and BMP-7.

Heat-related injury in lambs

The broad spectrum of heat-related injury (HRI) and its associated lesions is well described in the human literature, with rare reports of similar findings in farm animals. In the current case series, lesions from 4 of 8 lambs that presented with clinical signs of heat stress are reported. Gross lesions at necropsy consisted of acute renal swelling and pallor in 2 of 4 lambs, muscle pallor in 2 of 4 lambs, and chronic bronchointerstitial pneumonia in each of the 4 lambs. Histological lesions considered heat-related included acute renal tubular necrosis, pigment casts, tubular epithelial regeneration, multifocal myocyte degeneration, necrosis, and dropout with histiocytic influx and regeneration. Chronic, bronchointerstitial pneumonia, present in each lamb, was considered a condition predisposing to HRI. Compatibility between observed lesions and those reported in human beings with injury secondary to elevated body temperatures established a diagnosis of HRI in these animals. Diagnostic pathologists should consider HRI in lambs with histological evidence of renal tubular necrosis and/or rhabdomyolysis and even in cases where the clinical picture is strongly suggestive but lesions are not demonstrable.

Involvement of endogenous prostaglandin E2 in tubular epithelial regeneration through inhibition of apoptosis and epithelial-mesenchymal transition in cisplatin-induced rat renal lesions.

In the kidney, prostaglandin (PG) E2 is the main PG, playing important roles in maintaining homeostasis or development of pathological settings. Roles of PGE2 in renal lesions remain to be clarified. The expression patterns of PGE2 synthesis enzymes such as cyclooxygenase (COX)-1, COX-2 and microsomal PGE synthase (mPGES)-1, and PGE2 receptors (EP2 and EP4) were examined in cisplatin-induced rat renal failure. The immunoexpressions for COX-1, mPGES-1 and EP4 receptor were increased exclusively in the affected renal tubules, but those of COX-2 and EP2 receptor were not detected; increased expression of COX-1 was confirmed at mRNA level. Using rat renal epithelial cell line (NRK-52E), the effects of PGE2 on cell proliferation were investigated. The addition of PGE2 or 11-deoxy-PGE1 (EP4 receptor agonist) to NRK-52E increased the cell number, indicating the effects of PGE2 via EP4 receptor. Furthermore, 11-deoxy-PGE1-treated NRK-52E cells underwent the G0/G1 arrest and decreased apoptosis. NRK-52E treated with transforming growth factor (TGF)-beta1, an inducer of epithelial-mesenchymal transition (EMT), in the presence of 11-deoxy-PGE1 decreased the mRNA expression of alpha-smooth muscle actin (a marker of myofibroblasts). Collectively, the present study shows that COX-1 plays more important roles than dose COX-2 in cisplatin-induced rat renal failure; the product, PGE2, may regulate renal epithelial regeneration via EP4 receptor through inhibition of apoptosis and EMT.

Histopathologic study on the effects of methionine in reduction of nephrotoxicity due to co-administration of gentamicin and indomethacin in rats

Gentamicin is a wide spectrum aminoglycoside used against gram negative bacterial infections, but its clinical utility is restricted due to nephrotoxicity.Indomethacin is one of the NSAIDs with side effects on Kidney. Co-administration of indomethacin and gentamicin is necessary in some cases and may exaggerate gentamicin nephrotoxic effects. L-methionine can reduce gentamicin nephrotoxicity, so it may protect kidney from gentamicin and indomethacin co-administrative side effects.In this research, 42 male Sprague dawley rats were divided randomly into 6 equal groups. In the period of 14 days group 1-6 received normal saline (I.P),gentamicin (80 mg/kg BW, intramuscularly (I.M)), indomethacin ( I.M), gentamicin (I.M) plus indomethacin (I.M), L-methionine ( I.P),and gentamicin (I.M) plus indomethacin (I.M)and L-methionine(I.P) respectively once a day. In day 15, rats were euthanized and histopathologic slides of the kidneys were prepared.Histopatho logic examination revealed renal congestion, severe acute tubular necrosis, interstitial nephritis, glomerular atrophy and tubular dilatation in cortex in group 2. Glomerular hypercellularity was seen in group 3. In group 4, renal congestion, severe acute tubular necrosis,interstitial nephritis, glomerular hypercellularity and hyaline casts were seen. In group 5, medullary congestion and in group 6, renal congestion, tubular epithelial regeneration and normal tubules were seen. There was no microscopic lesion in group 1. The results of the present study showed that co-administration of gentamicin and indomethacin caused severe nephrotoxicity and L-methionine could ameliorate this effect.

Erythropoietin administration protects against functional impairment and cell death after ischaemic renal injury in pigs

To determine whether the administration of erythropoietin at the time of ischaemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial regeneration and promotes renal functional recovery, as it does in rodent models, in a higher mammalian model. The model of IRI involved unilateral nephrectomy in pigs, followed a week later by renal artery occlusion for 1 h, followed by reperfusion for 5 days. Pigs were randomized to receive erythropoietin 5000 units/kg intravenously at the time of ischaemia, followed by 1000 units/kg subcutaneously daily, or no treatment (six pigs each). Renal function and structure were analysed; blood and urine were collected daily to determine serum creatinine level, blood urea nitrogen, and creatinine clearance. Animals were killed after 5 days to obtain the injured kidneys. The kidneys were examined histologically for evidence of cellular mitosis, apoptosis and necrosis. Erythropoietin significantly abrogated renal dysfunction after IRI compared with controls at 12 h after injury; the mean (sem) creatinine clearance (as a percentage of baseline) for IRI was 68.2 (6)% vs erythropoietin-IRI 94.9 (8.9)% (P = 0.027), although by 36 h this was no longer significant, with values of 73.8 (12.7)% vs 95.9 (12)%, respectively (P = 0.23). Erythropoietin also significantly reduced the amount of cell death on histological analysis after 5 days of reperfusion, with a median (range) for IRI of 5.5 (1-45) vs erythropoietin-IRI of 1.5 (0-4) (P = 0.043). This study confirms the potential clinical applications of erythropoietin as a novel therapeutic agent in patients at risk of IRI.

Delayed administration of darbepoetin or erythropoietin protects against ischemic acute renal injury and failure

Administration of human recombinant erythropoietin (EPO) at time of acute ischemic renal injury (IRI) inhibits apoptosis, enhances tubular epithelial regeneration, and promotes renal functional recovery. The present study aimed to determine whether darbepoetin-alfa (DPO) exhibits comparable renoprotection to that afforded by EPO, whether pro or antiapoptotic Bcl-2 proteins are involved, and whether delayed administration of EPO or DPO 6 h following IRI ameliorates renal dysfunction. The model of IRI involved bilateral renal artery occlusion for 45 min in rats (N = 4 per group), followed by reperfusion for 1-7 days. Controls were sham-operated. Rats were treated at time of ischemia or sham operation (T0), or post-treated (6 h after the onset of reperfusion, T6) with EPO (5000 IU/kg), DPO (25 mug/kg), or appropriate vehicle by intraperitoneal injection. Renal function, structure, and immunohistochemistry for Bcl-2, Bcl-XL, and Bax were analyzed. DPO or EPO at T0 significantly abrogated renal dysfunction in IRI animals (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.08 +/- 0.03 mmol/l vs EPO-IRI 0.04 +/- 0.01 mmol/l, P = 0.01). Delayed administration of DPO or EPO (T6) also significantly abrogated subsequent renal dysfunction (serum creatinine for IRI 0.17 +/- 0.05 mmol/l vs DPO-IRI 0.06 +/- 0.01 mmol/l vs EPO-IRI 0.03 +/- 0.03 mmol/l, P = 0.01). There was also significantly decreased tissue injury (apoptosis, P < 0.05), decreased proapoptotic Bax, and increased regenerative capacity, especially in the outer stripe of the outer medulla, with DPO or EPO at T0 or T6. These results reaffirm the potential clinical application of DPO and EPO as novel renoprotective agents for patients at risk of ischemic acute renal failure or after having sustained an ischemic renal insult.

Heat shock proteins and acquired resistance to uranium nephrotoxicity

Previous studies have demonstrated that prior exposures to uranium can produce acquired resistance to uranium nephrotoxicity. In this study, the potential role for heat shock proteins (Hsps) in acquired resistance to uranium nephrotoxicity was explored. Pretreatment of male Sprague-Dawley rats with a conditioning dose of uranyl acetate (5 mg/kg, i.p.) was found to diminish the severity of proximal convoluted tubule necrosis and azotemia produced by a subsequent, higher uranyl acetate dose (10 mg/kg, i.p., 10 days after the conditioning dose). Kidney homogenates from rats euthanized at the end of the conditioning period were found to contain elevated levels of Hsp25, Hsp32, and Hsp70i, but not Hsc70. Immunochemical staining of renal sections for Hsp25 and Hsp70i revealed that these proteins were prominently expressed in tubular epithelial cells in uranyl acetate pretreated animals. Morphological characteristics and staining for proliferating cell nuclear antigen (PCNA) indicated that the cells expressing high levels of Hsps were regenerating. In RK3E and LLC-PK1 renal epithelial cells in culture, Hsp induction by thermal pretreatment did not afford protection from uranyl acetate cytotoxicity. Further, treatment of RK3E and LLC-PK1 cells with uranyl acetate did not result in induction of Hsps, as occurs with other nephrotoxic heavy metals. These observations suggest that while stress proteins are elevated in acquired resistance to uranyl acetate in vivo, they are not responsible for diminished uranium nephrotoxicity but are an epiphenomenon of tubular epithelial regeneration.

Renal expression and activity of the germinal center kinase SK2.

Rat fetal kidney mRNA was analyzed by RT-PCR to identify protein kinases. This screening demonstrated expression of a protein kinase consistent with SK2, a group II germinal center kinase and homolog of human Ste20-like kinase (SLK). SK2 mRNA, protein expression, and kinase activity were increased in rat fetal kidney homogenates (embryonic days 17-21) compared with adult controls. In adult kidneys subjected to cross-clamping of the renal artery, followed by reperfusion, SK2 mRNA, protein expression, and kinase activity were increased compared with untreated contralateral controls. By immunohistochemistry, SK2 expression was evident mainly in the cytoplasm of tubular epithelial cells in fetal and adult kidneys. There was also some expression in developing and mature podocytes, but staining of the interstitium was negative. In cultured renal tubular epithelial cells, SK2 kinase activity was increased after incubation with serum, or after exposure to chemical anoxia plus reexposure to glucose. Stable overexpression of SLK reduced cell proliferation and increased apoptosis and exacerbated apoptosis and necrosis after chemical anoxia plus reexposure to glucose. Thus SK2 is a renal epithelial protein kinase whose expression and activity are increased during development and recovery from acute renal failure, where tubular epithelial regeneration may recapitulate developmental processes. The actions of SK2 appear to be antiproliferative and may facilitate cell injury.

Connective tissue growth factor expression in the rat remnant kidney model and association with tubular epithelial cells undergoing transdifferentiation.

Connective tissue growth factor (CTGF) has been shown to mediate many actions of transforming growth factor-beta (TGF-beta) in the fibrotic response in several diseases. We compared expression of CTGF, TGF-beta, platelet-derived growth factor (PDGF), TNF-alpha, and interleukin-1 (IL-1) by in situ hybridization in Sprague-Dawley rats euthanized at 0, 2, 4, and 8 weeks after 5/6 nephrectomy using the rat remnant kidney model of renal failure. Collagen was evaluated by trichrome stains, immunohistochemistry, and electron microscopy. We compared expression patterns to cells undergoing metaplasia. Tubular epithelial regeneration and transdifferentiation to myofibroblasts were assessed morphologically and by proliferating cell nuclear antigen, smooth muscle actin, desmin, and vimentin immunohistochemistry. CTGF expression was minimal in controls, mild at 2 weeks and marked by 4 to 8 weeks in interstitial fibroblasts, coinciding with damage, regeneration, and fibrosis. TGF-beta expression was increased in many cell types at 2 weeks, increased further by 4 weeks, then remained constant. PDGF-B messenger RNA was found in many stromal cells at 2-4 weeks, but expression decreased at 8 weeks. No significant IL-1 or TNF-alpha staining was detected. We conclude that CTGF and interacting factors are associated with development or progression of chronic interstitial fibrosis. Proximity of CTGF, TGF-beta, and PDGF mRNA expression to regenerative epithelial cells and those transdifferentiating to myofibroblasts suggests that growth factors may modulate renal tubular epithelial differentiation.

A 4-WEEK ORAL TOXICITY STUDY OF PRULIFLOXACIN (NM441) IN DOGS FOLLOWED BY A 4-WEEK RECOVERY TEST

A repeated dose toxicity study of prulifloxacin, a new antibacterial agent, was conducted in beagle dogs. Male and female dogs were given the test material orally for 4 weeks at doses of 0 (control), 30, 150 and 750 mg/kg. After discontinuation of the treatment, a 4-week recovery test was also conducted. Feces containing white material were seen in the 150 and 750 mg/kg groups. Salivation, prone, lateral or sitting position, gait disturbance, and locomotor depression were observed in the 750 mg/kg group. In this dose group, decreased body weight and food and water consumptions were also observed. There were no treatment-related effects on survival. Ophthalmoscopic and electrocardiographic examinations and urinalysis failed to show any abnormalities related to the treatment. Hematologic examination showed decreased WBC in the 750 mg/kg group. Blood chemical examination revealed increased GPT and alpha 2-globulin in the 750 mg/kg group. Pathological changes caused by the treatment were as follows. Rarefaction of matrix, cavitations and erosions in humeral and femoral articular cartilages, and inflammatory cell infiltration in synovium were seen in the 150 and 750 mg/kg groups. Focal hemorrhage in synovium was also observed in the 750 mg/kg group. In kidney, regeneration of tubular epithelium, inflammatory cell infiltration, fibrosis and crystalline substance in the tubular lumen were observed in the 750 mg/kg group. The above-mentioned changes were satisfactorily reversible except for the changes in the humeral and femoral articular cartilages and in the kidney. Plasma levels and urinary concentrations of active metabolite of the test material were increased in all dose groups with dose-related manner, whereby no sex difference was observed. No effects caused by the repeated dosing were seen in the plasma concentrations. Toxicological findings were not observed in the 30 mg/kg group. The results show that the NOAEL of prulifloxacin is 30 mg/kg for 4-week repeated dose toxicity in dogs.

Evolving role of growth factors in the renal response to acute and chronic disease.

The roles of growth factors in the pathogenesis of various forms of acute and chronic renal disease are largely putative. Nevertheless, there is a growing body of information that links specific growth factors to particular forms of renal injury. In all instances, it is supposed that such associations are not necessarily unique and that multiple cytokines probably interact to determine the pattern of injury or the regenerative response to such injury. Regeneration of tubular epithelium after acute tubular necrosis involves upregulation of the epidermal growth factor (EGF) receptor. Early studies of exogenously administered EGF indicate that the severity and duration of renal failure may be attenuated by this growth factor. Thus far, the observed responses have been limited and the role of EGF as a therapeutic agent requires more study. The mechanism of generation of tubulointerstitial injury in most forms of renal disease is difficult to understand. Early in vitro studies of growth factor production by tubular cells (in the absence of any infiltrating cells) indicate that platelet-derived growth factor produced by the medullary collecting duct is mitogenic for renal medullary fibroblasts, suggesting a paracrine growth system in this region of the kidney. Insulin-like growth factor I has also been shown to be produced by collecting duct cells. Its production is increased by EGF, and its association with certain forms of renal hypertrophy, i.e., diabetes and hypersomatotrophic states, implies its participation in the hypertrophic growth response. Platelet-derived growth factor is a potent mitogen for glomerular mesangial cells, and its production is regulated by a variety of cytokines.(ABSTRACT TRUNCATED AT 250 WORDS)

Citrinin mycotoxicosis in the rat. I. Toxicology and pathology

In a series of four trials, citrinin was administered by the ip route as a single dose or in daily doses to determine its acute toxicity for the rat. The single dose LD 50 (Trial I) for citrinin dissolved in equal parts by volume of dimethylsulphoxide and 50% ethanol was 64 mg/kg body weight. Administration of this LD 50 dose after seven daily doses of either 32 or 48 mg citrinin/kg body weight killed only one of 19 rats (Trial II). In Trial IV, rats were killed 3, 6, 12, 24, 36 and 48 hr after receiving a single ip dose of 50 mg citrinin/kg for examination of kidneys and other tissues. The principal gross and microscopic alterations in the citrinin-treated rats were in the kidneys. Vacuolar degeneration of the renal tubular epithelium found 3 hr after treatment had progressed to extensive necrosis 33 hr later. Necrosis was the dominant lesion 36-72 hr after treatment. Regeneration of tubular epithelium, characterized by an increase in the nuclear to cytoplasmic ratio and the presence of cytoplasmic basophilia, was minimal 72 hr after treatment, but was prominent after 144 hr (Trial III).

THE HISTOPATHOLOGY OF INFECTIOUS BRONCHITIS IN FOWLS INFECTED WITH A NEPHROTROPIC “T” STRAIN OF VIRUS

The histopathology of the infectious bronchitis caused by the Cumming "T" strain of virus is described in fowls exposed to infection by an aerosol method. Desquamation of the ciliated and glandular epithelium throughout the trachea was seen 24 hours after exposure to virus. This was followed by rapid proliferation presumably of residual basal cells with the production of a stratified undifferentiated epithelial covering. Small areas of the tracheal submucosa showed lymphocytic infiltration by the 4th day. Cilia were first observed in the regenerating epithelium on the 7th day when mucous cells were also seen to be numerous. Alveolar mucous glands developed over the following 4 days and by the 12th day regeneration appeared complete. Pulmonary lesions were generally not severe and the air sacs were only slightly oedematous for 4 days following exposure. Necrosis of a few tubules scattered throughout the kidneys was seen on the 4th day. By the 6th day cystic tubules containing epithelial debris and polymorphonuclear leukocytes were prominent in both cortex and medulla and necrotic tubules were scattered throughout the kidneys. PAS positive granules were present in the renal tubular epithelium and were most pronounced in the distal convoluted tubules. Infiltration of the interstitium by lymphocytes and plasma cells was generally marked on the 7th day. The cytoplasm of these plasma cells was strongly PAS positive and such cells were most numerous on the 12th and 13th days after exposure and then their numbers rapidly declined. Regeneration of tubular epithelium was advanced by the 10th day and much of the cell debris had been cleared from the lumina of the tubules. What appeared to be compressed areas were seen in the cortex from the 13th day where glomeruli and tubules were numerous through considerably reduced in size. These were not seen after the 35th day, however an occasional lymph nodule persisted in the intersitium.

Renal lesions in the rabbit after long-term exposure to cadmium.

Renal lesions were produced in rabbits by subcutaneous injections of cadmium chloride in amounts of 0.25 mg/kg of body weight five days a week. Exposure for 11 and 17 weeks resulted in mild alterations in proximal tubular epithelial cells. Exposure for 23 and 29 weeks gave more profound tubular changes and sometimes mild glomerular alterations. Large deposits of metal were seen, especially in the proximal segments of the tubular epithelial cells, a small part of these were iron deposits. Degenerative changes were slight and signs of tubular epithelial regeneration were evident in rabbits examined 30 weeks after a 24-week exposure period. The metal deposits were still of the same magnitude as in rabbits examined after 23 and 29 weeks. The results from histologic examinations correlate with the results from investigations of kidney function in these rabbits.

Regeneration of Tubular Epithelium in the Human Kidney Following Injury by Mercuric Chloride

Excerpt It IS rather generally believed that the functional epithelium of the human kidney has only a limited regenerative capacity and that the clinical importance of this is negligible. The matte...