{"id":50330,"date":"2023-09-30T11:52:12","date_gmt":"2023-09-30T11:52:12","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=50330"},"modified":"2023-10-07T08:29:21","modified_gmt":"2023-10-07T08:29:21","slug":"a-review-on-animal-models-of-chronic-kidney-disease-an-update","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no3\/a-review-on-animal-models-of-chronic-kidney-disease-an-update\/","title":{"rendered":"A Review on Animal Models of Chronic Kidney Disease- An Update"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Chronic\nkidney disease is defined as abnormalities of kidney structure or function,\npresent for greater than 3 months. This is defined as a GFR less than 60\nmL\/min\/1.73 m2 or one or more markers of kidney dysfunction including\nalbuminuria.The pathophysiological mechanism underlying CKD includes initial\ntrigger mediated through inflammation or immunological response or a toxicant. Hyper\nfiltration and hypertrophy occurs later that contributes to progression of\nkidney damage (1).All these eventslead to secondary complications like\ndiabetes, cardiac diseases, stroke, etc. (2). The increase in number of CKD\ncases is linked with the aging, increased prevalence of diabetes mellitus and\nhypertension,diabetesmellitus being the leading\ncause(3,4).CKD is believed to affect 10% to 15% of the population and is\nestimated to contribute to 5 to 10 million deaths annually(5). It is also\nobserved that CKD imparts cardiovascular burden in the patients that may be\nbecause of intimal, medial and valvular calcification of arteries(5,6).The\nabnormal toxins accumulation in CKD patients can cause imbalances in renin\nangiotensin aldosterone system causing increased blood pressure, increased\ncoagulation that in turn may pose a threat of myocardial infarction culminating\nin heart failure. This pathway is known as Cardio-renal syndrome(7).The\nfindings from several studies also prove the linkage between CKD, small blood\nvessel diseases of cerebrum and impairment of cognition but the pathological\nmechanisms remain unclear(8). The non-specific interventions in established CKD\nresult in reduction of the disease progression. Also, Early investigations\nthrough imaging and biopsy techniques and Targeting Specific underlying cause\nis also crucial for delivering proper care in the patients with CKD.\nRenoprotective agents- Angiotensin-converting enzyme II inhibitors and\nangiotensin II receptor blockers are considered as first line drugs in CKD\nirrespective of the underlying causes(both diabetic and non-diabetic). Drugs\ntargeting renal fibrosis are still under investigations that can be promising\nagents for CKD treatment. Dietary sodium restriction and diuretic therapy\nreduce the fluid overload. Oral alkali therapy with sodium bicarbonate (1.5 to\n3.0 g\/day) slows the rate of progression(9). Impairment of immune response in\nCKD either leads to increased risk of infections where as exaggeration leads\ntoinflammation along with its after effects. Targeting these immune\nabnormalities can also be an effective strategy in advanced CKD(10).<\/p>\n\n\n\n

Understanding\nthe underlying mechanisms for the development and progression of kidney\ndiseases is important for finding the new treatments in this context. For\nachieving these goals both rodent and non rodent models are proven to be\nvaluable investigating tools. Rodents, especially Rats are able to replicate\nthe human histological manifestations of kidney diseases to larger extent\nmaking them as useful options(11). The present review focuses on animal models\nof CKD <\/p>\n\n\n\n

Hypertension model of CKD<\/strong><\/p>\n\n\n\n

Hypertension is considered to be a cause and outcome of CKD, characterized by proteins in urine and sclerosis of glomeruli. This leads to reduced glomerular filtration. The histology of hypertensive CKD ischaracterized by renal inflammation and interstitial fibrosis (12).<\/p>\n\n\n\n

Spontaneously hypertensive rat model<\/strong><\/p>\n\n\n\n

8-week-old male spontaneously hypertensive rats(SHR) can serve as better tool for understanding hypertension induced kidney injury (13). The uninephrectemised SHR rats are observed over a period of 40 weeks in presence or absence of drug treatments and at the end of 40th<\/sup> week, the urine samples are collected.The animals are then sacrificed; blood samples are collected followed by dissection of kidneys. Biochemical, histological and immunohistochemistry studies are performed. It is believed that in these models microinflammation is the cause of renal injury(14). Proteinuria, glomerulosclerosis, and interstitial fibrosis are observed. The pathology can be exaggerated by introducing high salt diet especially in male SHR rats (15). Oxidative stress appears in the beginning followed by inflammation(16).<\/p>\n\n\n\n

5\/6th<\/sup>Nephrectomy model<\/strong><\/p>\n\n\n\n

Often called as sub total nephrectomy, is the best model for studying progressive renal failure with loss of renal mass(17). Tissue ablation or ligation of renal tissue induces renal failure(18). 12- weeks after establishing the model, drastic increase in blood urea nitrogen and proteinuria can be observed(19). This method requires expertise in surgical procedures.Nephrectomy-induces systolic arterial hypertension and thereby cause changes in remnant kidney tissue both structurally and functionally. Structural changes include glomerular hypertrophy, mesangial expansion, glomerular sclerosis, interstitial fibrosis and tubule-interstitial atrophy(20). This model is considered as an established model for glomerulonephritis and renal fibrosis especially in female wistar rats (21).<\/p>\n\n\n\n

Deoxycorticosterone acetate salt hypertension induced model of CKD<\/strong><\/p>\n\n\n\n

Deoxycorticosterone acetate salt induces\nhypertension by increasing expression of TNF alpha there by increasing\ninflammation in renal tissue (22). This is a model of primary aldosteronism\nthat also induces oxidative stress and renal fibrosis (23).Uninephrectomy\nperformed 8 weeks old Sprague Dawley rats are given access to NaCl; and DOCA\nsalt is administered subcutaneously that develop hypertension and fibrosis (24).\nThis model lasts only for 8-12 weeks.so not a popular choice for modelling CKD.<\/p>\n\n\n\n

Diabetic Nephropathy\nmodel of CKD<\/strong><\/p>\n\n\n\n

Diabetic nephropathy is the leading cause of\nCKD worldwide. It is characterized by renal inflammation and fibrosis, tissue\nremodeling along with oxidative stress (25,26). Glomerulosclerosis\nis also a characteristic feature of diabetic nephropathy, reflecting the\naccumulation of \u03b1-smooth muscle actin \nand the epithelialmesenchymal transition. Diabetes can be induced by single intraperitoneal injection\nof 45mg\/kg of Streptozotocin in 8-week old SD rats. Increased weight of\nkidneys, blood glucose, alanine transaminase, aspartate transaminase, catalase,\nsuperoxide dismutase and glutathione are the parameters to be assessed(27).\nTransforming Growth Factor-\u03b21 is deemed to take a vital part in the deposition\nof Extracellular matrix, serum creatinine and blood urea nitrogen (BUN) levels\nin Diabetes(28). Addition of high fat diet to Steptozotocin can mimic human\ntype 2 diabetes(insulin resistance). SD rats are fed with high fat diet\ncontaining 50 % fat in food for 9 weeks. Streptozotocin (35mg\/kg) is injected\ni.p. at 4th<\/sup> and 6th<\/sup> week then plasma and renal parameters\ncan beevaluated(29).<\/p>\n\n\n\n

The\nAkitaIns2+ <\/sup>mice that has spontaneous point mutation in preproinsulin\ngene produces Type 1 Diabetes by direct pancreatic  beta cell toxicity is a model for studying\nprogressive events of kidney disease including mesangial expansion and\nalbuminuria. Non obese diabetic mice is characterized by autoimmune destruction\nof beta cells of pancreas thus produces renal injury in 40days due to mesangial\nexpansion and podocyte loss. New Zealand Obese mouse (Type 2 diabetes along\nwith obesityrelated to leptin resistance),Ob\/ob,\ndb\/db<\/em> and Zucker fatty rat models can be useful for studying Diabetic\nNephropathy (30).<\/strong><\/p>\n\n\n\n

Drug induced Chronic\nKidney disease<\/strong><\/p>\n\n\n\n

As surgical methods possess risk of mortality among the animals in the study, the use of inducing agents to produce chronic nephrotoxicity is considered as desired and beneficial option.<\/p>\n\n\n\n

Adriamycin induced CKD<\/strong><\/p>\n\n\n\n

Adriamycin induces nephropathy similar to renal injury in humans. Glomerular damage, increased proteins in urine, segmental sclerosis and tubular interstitial fibrosis are the sequeale of renal events associated with adriamycin. All these events occur 6weeks after a single intravenous injection of Adriamycin (5mg\/kg) in male albino rats (31, 32) or 20mg\/kg i.p. in wistar rats(33). Adriamycin causes podocyte injury followed by expression of transforming growth factor beta-1 associated with glomerulosclerosis, depletion of podocytes and decreased renal function (34).<\/p>\n\n\n\n

Adenine-induced model of CKD<\/strong><\/p>\n\n\n\n

This model is first explained in 1986 by Yokozawa et al. and is\nvery much adopted in recent studies. Adenine when given either with diet or\nvehicle causes occlusion of renal tubules, ischemia and\nfinally fibrosis leading to CKD progression and retardation of growth\nwhich is more relevant to CKD in human (35). In initial models, 0.75%w\/w of\nadenine was given with diet, this is later modified to 0.5 or 0.25% w\/w. Diet\ncontaining 0.25% adenine\nwhen fed for 35days in 9-10 weeks old Sprague Dawley rats, produces progressive\nCKD. Adenine increased plasma concentrations of inflammatory cytokines and\ndecreased antioxidant levels(36,37) serum blood urea nitrogen, creatinine and\nuric acid are found to be increased with adenine diet(38). Adenine model is\nmore advantageous over surgical model of CKD as it reduces mortality and\ninter-species difference during experimentation(39).<\/p>\n\n\n\n

CKD in Aging rats<\/strong><\/p>\n\n\n\n

Aging is characterized by proteinuria, lesions\nin tubularinterstitium and cell damage. Thus is an important factor for development\nof end stage renal disease (40). Endoplasmic Reticulum stress and apoptosis are\nconsidered as the contributing factor for tubular cell injury. Rodents older\nthan 20 to 24 months are considered to be aged and are suitable for the study (41).\nShort term high fat diet fed aged Sprague Dawley rats for 15 days can produce renal\ninflammation and fibrosis (42).<\/p>\n\n\n\n

Autoimmune Chronic Kidney disease<\/strong><\/p>\n\n\n\n

Kidney can be target of autoimmunity resulting\nin nephritis caused by systemic lupus erythematosus in 35-55% of patients because\nof abnormal glomerular inflammation (43). Lupus\nNephritis, that is one of the serious complication of Systemic Lupus\nErythematosus causes activation of inflammatory cells and proliferation of\nlocal tissue that stimulate chemokine and cytokine release(44). Nephritis induced by IgA causes\nhematuria and glomerulonephritis involving mesangial cells. IgG anti-IgA\nformation induces inflammation that causes kidney failure (45). Heymann\nNephritis is another form of immune mediated injury of glomerulus often termed\nas membraneousglomerulo-nephropathy. Its active model is produced by injection\nof isolated brush border components of rat\u2019s proximal tubules into Lewis or\nfisher rats. Within 3 to 4 weeks, IgG deposition occur in glomerulus and proteinuria\ndevelops in 8-weeks(46). Whereas in passive model, antisera produced from\nantigen of another animal is injected to exhibit immune response (47).\nInjection of rabbit or mouse thymocyte serum through tail vein induces membrano\nproliferative glomerulonephritis that causes proliferation of mesangial cells\nand proteinuria with in 1-week. This model repairs on its own after 3 weeks\nwhereas repeated injections cause progressive chronic kidney disease (12). Anti- Glomerular Basement Membrane model is another\nmodelof glomerulonephritis induced by active immunization with isolated or\nrecombinant collagen IV or by injection of anti GBM antibodies passively in\nWistar Kyoto Rats (48,49).<\/p>\n\n\n\n

Hereditary or genetic\nmodels of CKD<\/strong><\/p>\n\n\n\n

Alport\nsyndrome is an inherited genetic disease that occurs due to mutation in genes\nencoding collagen IV \u03b15 chain(COL4A5<\/em>).\nAccumulation of these chains occurs in glomerular basement membrane and alters\nits function. The development of nephropathy is same in both sexes(50). Initially\nit is manifested as hematuria. Further collagen signallings causes albuminuria\nthat further contribute to renal fibrosis(51). Polycystic kidney disease is hereditary disorder  characterized by abnormal cell proliferation,\nfluid accumulation, inflammation and renal fibrosis. Two types of Poly cystic\nkidney diseases include, Autosomal dominant polycystic kidney diseases and\nAutosomal recessive\npolycystic kidney diseases (52). Autosomal dominant polycystic kidney\ndiseases is one of the common genetic cause of renal disease. It is\nassociated with mutations in genes of polycystic kidney disease (PKD1 &\nPKD2). The Han:SPRD-Cy rat strain is one of the spontaneous hereditary\nmodel for PKD characterized by large number of cysts formed by missense\nmutations. Another rodent model includes, PCK rats that are discovered from\nSprague Dawley rats outbreeding, Pkhd1 being the responsible gene. Pcy(polycystic) mouse derived from KK strain produces\nmissense mutation in gene similar to human Nphp3 is also one of the hereditary\nmodel for PKD(53). Crj:CD\/SD is another homozygous mutant\nmodel for PKD that develop renal cysts within one week after birth where asbpk<\/em> (BALB\/c polycystic kidney) mice model, homozygous mutants develop renal\ncysts and die within 4 weeks after birth. Although many models of PKD share\nsimilar pathological features of end stage renal diseases, understanding\nmolecular mechanisms and identifying novel drug targets still remain as a\nchallenge.(54)Podocyte-specific\ngenetic model for focal segmental glomerular sclerosis(Nep 25 mice) is produced\nby administration of immunotoxin specific to podocytes under nephrin promoter\nin mouse causing intraglomerular injury. Human immunodeficient virus associated\nNephropathy, is produced in Tg26 mice (it has replication deficient HIV\ntransgene) characterized by severe proteinuria, ascites, low levels of urinary\nalbumin and mesangial hyperplasia especially on FVB\/N, C57BL\/6, 129\/Sv \nstrain backgrounds (55).<\/p>\n\n\n\n

Recently role of Sirtuins in development of renal\ndiseases has gained attention. Various body organs especially kidneys are vulnerable\nto age related damage and also injuries occurring due to toxic substances.\nSilent information regulators are NAD+ <\/sup>dependent deacetylases(\nconsisting of 7 isoforms-SIRT1 to SIRT7). SIRT1 gene is highly expressed in\nnucleus and cytoplasm of fetal and adult tissues like Liver, Kidney, Brain.  High glucose concentrations can increase\nexpression of p53 and cleaved caspase-3 in renal epithelium. This stimulates\nexpression of SIRT1 by medullary mesenchymal cells that inturn reverses the p53\nlevels. Thus SIRT1 inhibits podocyte apoptosis.Thus SIRT1 has a significant\nrole in Diabetic kidney disease. Additionally it regulates the TGFbeta\/Smad\npathway thereby inhibits kidney fibrosis. It also has role in regulation of\nrenal inflammation in diabetic nephropathy through TNF alpha and COX-2 gene\ndownregulation. Thus upregulation of SIRT1 activity can inhibit renal cell\napoptosis.(63,64,65) Podocyte-specific Sirt1 knockout mice model is useful to\nstudy the role of sirtuins in Diabetic nephropathy where it inactivates p65 subunit\nof NF-kB and STAT3 and suppresses podocyte dysfunction.(66)<\/p>\n\n\n\n

In addition, Klotho, an antiageing gene has been\ninvolved with cellular senescence. Deficiency of klotho gene induces oxidative\nstress, associated with multiple disorders like atherosclerosis, infertility,\nosteoporosis, cognitive decline etc. Klotho deficient mice can be a useful tool\nfor studying premature ageing like syndrome-altered glucose, lipid and amyloid\nbeta metabolism.(67) Low klotho expression is associated with raised Fibroblast\ngrowth factor(FGF23) that causes advanced CKD associated with cardiovascular\ncomplications such as vascular calcification, Left ventricular atrophy and\ncardiac fibrosis.(68)<\/p>\n\n\n\n

Table 1: Animal models for chronic kidney diseases.<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

 <\/strong><\/p>\n<\/td>\n

\n

MODEL<\/strong><\/p>\n<\/td>\n

\n

ANIMAL\/STRAIN<\/strong><\/p>\n<\/td>\n

\n

CHANGES IN HISTOLOGY<\/strong><\/p>\n<\/td>\n

\n

REFERENCE<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

1<\/strong><\/p>\n<\/td>\n

\n

Hypertension models of CKD<\/strong><\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n<\/tr>\n

\n

A<\/strong><\/p>\n<\/td>\n

\n

Spontaneously hypertensive rat model:<\/strong><\/p>\n<\/td>\n

\n

7 to 8 weeks old male SHR rats<\/p>\n<\/td>\n

\n

Glomerulosclerosis, and interstitial fibrosis <\/p>\n<\/td>\n

\n

15,55,56<\/p>\n<\/td>\n<\/tr>\n

\n

B<\/strong><\/p>\n<\/td>\n

\n

5\/6 Nephrectomy model<\/strong>:<\/p>\n<\/td>\n

\n

Male Sprague\u2013Dawley rats, female wistar rats<\/p>\n<\/td>\n

\n

Mesangial expansion, glomerular sclerosis, interstitial fibrosis and tubule-interstitial atrophy.<\/p>\n<\/td>\n

\n

20,21,57<\/p>\n<\/td>\n<\/tr>\n

\n

C<\/strong><\/p>\n<\/td>\n

\n

Deoxycorticosterone acetate salt hypertension-induced model<\/strong><\/p>\n<\/td>\n

\n

8- weeks old Sprague Dawley rats<\/p>\n<\/td>\n

\n

renal fibrosis<\/p>\n<\/td>\n

\n

23,24<\/p>\n<\/td>\n<\/tr>\n

\n

2<\/strong><\/p>\n<\/td>\n

\n

Diabetic Nephropathy model of CKD<\/strong><\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n<\/tr>\n

\n

 <\/strong><\/p>\n<\/td>\n

\n

 <\/strong><\/p>\n<\/td>\n

\n

 8-week old SD rats(STZ 45mg\/kg I.P)<\/p>\n<\/td>\n

\n

Glomerulosclerosis<\/p>\n<\/td>\n

\n

27<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

Zucker fatty rat<\/p>\n<\/td>\n

\n

Renal interstitial fibrosis and glomerulosclerosis <\/p>\n<\/td>\n

\n

58<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

db\/db<\/em><\/p>\n<\/td>\n

\n

Glomerulosclerosis,<\/p>\n<\/td>\n

\n

59<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

Ob\/ob<\/em><\/p>\n<\/td>\n

\n

Podocyte apoptosis<\/p>\n<\/td>\n

\n

60<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

Non Obese mouse<\/p>\n<\/td>\n

\n

Glomerular lesions<\/p>\n<\/td>\n

\n

61<\/p>\n<\/td>\n<\/tr>\n

\n

3<\/strong><\/p>\n<\/td>\n

\n

Drug-induced Chronic Kidney disease<\/strong><\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n<\/tr>\n

\n

A<\/strong><\/p>\n<\/td>\n

\n

Adriamycin induced CKD<\/strong><\/p>\n<\/td>\n

\n

Adriamycin (5mg\/kg) in male albino rats. 20mg\/kg i.p. in wistar rats.<\/p>\n<\/td>\n

\n

Podocyte injury, glomerulosclerosis<\/p>\n<\/td>\n

\n

32,33<\/p>\n<\/td>\n<\/tr>\n

\n

B<\/p>\n<\/td>\n

\n

 Adenine-induced model of CKD<\/strong><\/p>\n<\/td>\n

\n

9-10 weeks old Sprague Dawley rats<\/p>\n<\/td>\n

\n

Renal fibrosis<\/p>\n<\/td>\n

\n

34<\/p>\n<\/td>\n<\/tr>\n

\n

4<\/strong><\/p>\n<\/td>\n

\n

CKD in Aging rats<\/strong><\/p>\n<\/td>\n

\n

24-months old male Sprague Dawley rats<\/p>\n<\/td>\n

\n

Tubularinterstitial lesions,<\/p>\n

Glomerulosclerosis<\/p>\n<\/td>\n

\n

40,55<\/p>\n<\/td>\n<\/tr>\n

\n

5<\/strong><\/p>\n<\/td>\n

\n

Autoimmune Chronic Kidney disease<\/strong><\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n<\/tr>\n

\n

A<\/p>\n<\/td>\n

\n

Lupus Nephritis<\/p>\n<\/td>\n

\n

MRL\/lpr<\/em> and NZB\/W mice<\/p>\n<\/td>\n

\n

Renal fibrosis<\/p>\n<\/td>\n

\n

55<\/p>\n<\/td>\n<\/tr>\n

\n

B<\/p>\n<\/td>\n

\n

IgA  induced Nephritis<\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

Mesangioproliferative glomerulonephritis<\/p>\n<\/td>\n

\n

55<\/p>\n<\/td>\n<\/tr>\n

\n

C<\/p>\n<\/td>\n

\n

Heymann Nephritis<\/p>\n<\/td>\n

\n

Lewis or fisher rats<\/p>\n<\/td>\n

\n

Membranous nephropathy <\/p>\n<\/td>\n

\n

62<\/p>\n<\/td>\n<\/tr>\n

\n

D<\/p>\n<\/td>\n

\n

Anti GBM Nephritis<\/p>\n<\/td>\n

\n

Wistar Kyoto Rats<\/p>\n<\/td>\n

\n

Membranous nephropathy <\/p>\n<\/td>\n

\n

49<\/p>\n<\/td>\n<\/tr>\n

\n

6<\/strong><\/p>\n<\/td>\n

\n

Hereditary or genetic models of CKD<\/strong><\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n<\/tr>\n

\n

A<\/p>\n<\/td>\n

\n

Alport syndrome<\/p>\n<\/td>\n

\n

Alport mice<\/p>\n<\/td>\n

\n

Tubularinterstitial lesions,<\/p>\n

Glomerulosclerosis<\/p>\n<\/td>\n

\n

55<\/p>\n<\/td>\n<\/tr>\n

\n

B<\/p>\n<\/td>\n

\n

Polycystic kidney disease<\/p>\n<\/td>\n

\n

Han:SPRD-Cy rat<\/p>\n<\/td>\n

\n

Intraglomerular injury<\/p>\n<\/td>\n

\n

53,54<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

 PCK rats<\/p>\n<\/td>\n

\n

Intraglomerular injury<\/p>\n<\/td>\n

\n

53,54<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

Pcy mouse<\/p>\n<\/td>\n

\n

Intraglomerular injury<\/p>\n<\/td>\n

\n

53,54<\/p>\n<\/td>\n<\/tr>\n

\n

 <\/p>\n<\/td>\n

\n

 <\/p>\n<\/td>\n

\n

bpk<\/em> (BALB\/c polycystic kidney) mice<\/p>\n<\/td>\n

\n

Intraglomerular injury<\/p>\n<\/td>\n

\n

53,54<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

Chronic kidney disease is becoming a common disease\nwith greater prevalence associated various etiologies, majorly with Diabetes\nand Hypertension. Immune mediated responses also account for many cases of CKD\nworldwide. Hence there is an immediate need for modeling kidney diseases that\napproximate to human pathology. Animal models, especially mice and rats are\nconvenient for evaluating the novel drugs in chronic kidney diseases. Even\nafter the discovery of various models for CKD, no single model exactly reflects\nhuman CKD. Strain, genetics and non-detectable effects of CKD can be\nlimitations of animal studies, Thus progressive efforts are put forward in this\ndirection to create new models or improve existing ones. Presence of\nco-morbidities, age, causative factors of kidney disease are to be taken into\nconsideration while designing new models. Further advancement in molecular biology\ntechniques are useful in understanding CKD molecular level pathogenesis and its\ncomplications which further aid in developing new transgenic models. The present review provides concise\ninformation on animal models of CKD along with their histological data for\ndiscovering new leads for CKD. <\/p>\n\n\n\n

Conflict of Interest<\/strong><\/p>\n\n\n\n

There are no conflicts of Interest.<\/p>\n\n\n\n

Funding Sources<\/strong><\/p>\n\n\n\n

There is no conflict of interest.<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

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