although several cases of glomerulonephritis with myeloproliferative neoplams ( mpn ) such as polycythemia vera ( pv ) or essential thrombocythemia ( et ) have been reported , the association between mpn and glomerulonephritis is still obscure .
paraffin sections from the biopsied specimens of the three cases were examined with hematoxylin and eosin , periodic acid - schiff , methenamine silver , and masson s trichrome stains .
immunoglobulins ( igg , iga , and igm ) , complement ( c3 and c1q ) , and fibrinogen were assessed by a direct immunofluorescence staining method on frozen sections for two cases and by immunostaining on paraffin sections for the other case .
, we also review previously reported cases in the english literature of renal glomerular disorders associated with mpn , which were examined by renal biopsy .
her condition was stable at diagnosis , but edema occurred 2  months later , upon which administration of hydroxyurea was initiated .
the patient s height , weight , and blood pressure were 150  cm , 50  kg , and 180/80  mmhg , respectively .
the laboratory data were as follows : hemoglobin , 15.8  g / dl ; hematocrit , 47.3  % ; platelets , 490,000/l ; white blood cells , 8,100/l , c - reactive protein , < 0.2  mg / dl ; blood urea nitrogen , 25.7  mg / dl ; serum creatinine , 1.2  mg / dl ; total cholesterol , 182  mg / dl ; total protein , 5.9  g / dl ; albumin , 3.1  g / dl ; globulin , 2.8  g / dl ; lactate dehydrogenase , 241  iu / l ; aspartate aminotransferase , 18  iu / l ; alanine aminotransferase , 12  iu / l ; total bilirubin , 0.3  mg / dl ; -glutamyl transpeptidase , 25 
iu / l ; na , 141  mmol / l ; k , 4.8  mmol / l ; and cl , 109  mmol / l .
1 ) ; 13 glomeruli could be evaluated , 2 of which exhibited global sclerosis .
immunohistological staining was positive for igg and iga with a granular pattern and negative for igm , c1q , c3 , and fibrinogen .
the patient was diagnosed with iga nephropathy with an active lesion , and treatment consisting of 30  mg prednisolone , 50  mg cyclophosphamide , and 80  mg telmisartan per day was started .
although treatment improved the proteinuria and hematuria , the patient s serum creatinine level remained unchanged .
c electron - dense deposits in the mesangial region a 62-year - old woman was admitted to our hospital because of general fatigue and chest discomfort .
she had experienced acute glomerulonephritis 6  years previously , but the details of the clinical course were not known .
proteinuria had been detected while she was pregnant , and she had been treated for hypertension for 15  years . she had been diagnosed with et at another hospital 3  years earlier .
no remarkable cardiac problems were found when she was examined at the department of cardiology after admission .
she was referred to the department of general medicine for a renal biopsy to investigate the persistent proteinuria . the patient s height , weight , and blood pressure were 148  cm , 55  kg , and 179/107  mmhg , respectively .
she did not have remarkable abnormalities in the lungs and abdomen and did not show pitting edema .
the laboratory data were as follows : hemoglobin , 11.4  g / dl ; hematocrit , 39.8  % ; platelets , 978,000/l ; white blood cells , 14,400/l ; c - reactive protein , < 0.2  mg / dl ; blood urea nitrogen , 15.8  mg / dl ; serum creatinine , 0.7  mg / dl ; total cholesterol , 227  mg / dl ; total protein , 7.3  g / dl ; albumin , 4.5  g / dl ; globulin , 2.8  g / dl ; lactate dehydrogenase , 811 
iu / l ; aspartate aminotransferase , 22  iu / l ; alanine aminotransferase , 11 
iu / l ; total bilirubin , 0.3  mg / dl ; -glutamyl transpeptidase , 21  iu / l ; alkaline phosphatase , 470 
iu / l ; na , 144  mmol / l ; k , 5.0  mmol / l ; and cl , 107  mmol / l .
urinalysis showed 4 + proteinuria ( 1.51  g / day ) and no evidence of hematuria .
2 ) , and 19 glomeruli could be evaluated , 2 of which exhibited global sclerosis .
c immunoglobulin m deposition in the mesangial region of a glomerulus identified by immunostaining 
  case 2 .
c immunoglobulin m deposition in the mesangial region of a glomerulus identified by immunostaining a 51-year - old man was admitted to our hospital for renal biopsy .
proteinuria had been detected when the patient was approximately 30  years of age , and he had experienced tonsillitis several times . the patient had been diagnosed with pv with an abnormality of the jak2 gene 3  years earlier .
renal biopsy was planned because his proteinuria had become more apparent over the past 2  years .
the patient s height , weight , and blood pressure were 165  cm , 66  kg , and 120/73  mmhg , respectively .
no remarkable abnormalities were found in the heart , lungs , or abdomen , and pitting edema was not observed .
the laboratory data were as follows : hemoglobin , 15.3  g / dl ; hematocrit , 48.1  % ; platelets , 326,000/l ; white blood cells , 8,400/l ; c - reactive protein , < 0.2  mg / dl ; blood urea nitrogen , 22.2  mg / dl ; serum creatinine , 1.4  mg / dl ; total cholesterol , 194  mg / dl ; total protein , 7.1  g / dl ; albumin , 4.1  g / dl ; globulin , 3.0  g / dl ; lactate dehydrogenase , 169  iu / l ; aspartate aminotransferase , 17  iu / l ; alanine aminotransferase , 23 
iu / l ; total bilirubin , 0.5  mg / dl ; -glutamyl transpeptidase , 21  iu / l ; alkaline phosphatase , 276 
iu / l ; na , 139  mmol / l ; k , 4.7  mmol / l ; and cl , 106  mmol / l .
urinalysis showed 4 + proteinuria ( 1.2  g / day ) and no evidence of hematuria .
.  3 ) and 22 glomeruli could be evaluated , 5 of which showed global sclerosis .
tonsillectomy plus steroid pulse therapy and an angiotensin ii receptor blocker were selected as treatments for the patient .
d electron - dense deposits in the paramesangial region 
  case 3 . a micrograph of the glomeruli showing mesangial proliferation .
her condition was stable at diagnosis , but edema occurred 2  months later , upon which administration of hydroxyurea was initiated .
the patient s height , weight , and blood pressure were 150  cm , 50  kg , and 180/80  mmhg , respectively .
the laboratory data were as follows : hemoglobin , 15.8  g / dl ; hematocrit , 47.3  % ; platelets , 490,000/l ; white blood cells , 8,100/l , c - reactive protein , < 0.2  mg / dl ; blood urea nitrogen , 25.7  mg / dl ; serum creatinine , 1.2  mg / dl ; total cholesterol , 182  mg / dl ; total protein , 5.9  g / dl ; albumin , 3.1  g / dl ; globulin , 2.8  g / dl ; lactate dehydrogenase , 241  iu / l ; aspartate aminotransferase , 18  iu / l ; alanine aminotransferase , 12  iu / l ; total bilirubin , 0.3  mg / dl ; -glutamyl transpeptidase , 25 
iu / l ; na , 141  mmol / l ; k , 4.8  mmol / l ; and cl , 109  mmol / l .
1 ) ; 13 glomeruli could be evaluated , 2 of which exhibited global sclerosis .
immunohistological staining was positive for igg and iga with a granular pattern and negative for igm , c1q , c3 , and fibrinogen .
the patient was diagnosed with iga nephropathy with an active lesion , and treatment consisting of 30  mg prednisolone , 50  mg cyclophosphamide , and 80  mg telmisartan per day was started .
although treatment improved the proteinuria and hematuria , the patient s serum creatinine level remained unchanged .
a 62-year - old woman was admitted to our hospital because of general fatigue and chest discomfort .
she had experienced acute glomerulonephritis 6  years previously , but the details of the clinical course were not known .
proteinuria had been detected while she was pregnant , and she had been treated for hypertension for 15  years . she had been diagnosed with et at another hospital 3  years earlier .
no remarkable cardiac problems were found when she was examined at the department of cardiology after admission .
she was referred to the department of general medicine for a renal biopsy to investigate the persistent proteinuria .
the patient s height , weight , and blood pressure were 148  cm , 55  kg , and 179/107  mmhg , respectively .
she did not have remarkable abnormalities in the lungs and abdomen and did not show pitting edema .
the laboratory data were as follows : hemoglobin , 11.4  g / dl ; hematocrit , 39.8  % ; platelets , 978,000/l ; white blood cells , 14,400/l ; c - reactive protein , < 0.2  mg / dl ; blood urea nitrogen , 15.8  mg / dl ; serum creatinine , 0.7  mg / dl ; total cholesterol , 227  mg / dl ; total protein , 7.3  g / dl ; albumin , 4.5  g / dl ; globulin , 2.8  g / dl ; lactate dehydrogenase , 811 
iu / l ; total bilirubin , 0.3  mg / dl ; -glutamyl transpeptidase , 21  iu / l ; alkaline phosphatase , 470  iu / l ; na , 144  mmol / l ; k , 5.0  mmol / l ; and cl , 107  mmol / l . urinalysis showed 4 + proteinuria ( 1.51  g / day ) and no evidence of hematuria .
2 ) , and 19 glomeruli could be evaluated , 2 of which exhibited global sclerosis .
c immunoglobulin m deposition in the mesangial region of a glomerulus identified by immunostaining 
  case 2 .
proteinuria had been detected when the patient was approximately 30  years of age , and he had experienced tonsillitis several times . the patient had been diagnosed with pv with an abnormality of the jak2 gene 3  years earlier .
renal biopsy was planned because his proteinuria had become more apparent over the past 2  years .
the patient s height , weight , and blood pressure were 165  cm , 66  kg , and 120/73  mmhg , respectively .
no remarkable abnormalities were found in the heart , lungs , or abdomen , and pitting edema was not observed .
the laboratory data were as follows : hemoglobin , 15.3  g / dl ; hematocrit , 48.1  % ; platelets , 326,000/l ; white blood cells , 8,400/l ; c - reactive protein , < 0.2  mg / dl ; blood urea nitrogen , 22.2  mg / dl ; serum creatinine , 1.4  mg / dl ; total cholesterol , 194  mg / dl ; total protein , 7.1  g / dl ; albumin , 4.1  g / dl ; globulin , 3.0  g / dl ; lactate dehydrogenase , 169 
iu / l ; aspartate aminotransferase , 17  iu / l ; alanine aminotransferase , 23 
iu / l ; total bilirubin , 0.5  mg / dl ; -glutamyl transpeptidase , 21  iu / l ; alkaline phosphatase , 276 
iu / l ; na , 139  mmol / l ; k , 4.7  mmol / l ; and cl , 106  mmol / l . urinalysis showed 4 + proteinuria ( 1.2  g / day ) and no evidence of hematuria .
tonsillectomy plus steroid pulse therapy and an angiotensin ii receptor blocker were selected as treatments for the patient .
according to the world health organization classification , mpns are classified into the following six diseases : pv , et , chronic myelogenous leukemia ( cml ) , primary myelofibrosis ( pmf ) , chronic neutrophilic leukemia ( cnl ) , and chronic eosinophilic leukemia / hypereosinophilic syndrome ( cel / hes ) .
most reports of glomerular disease associated with mpn have involved pv or et , whereas few reports have described associations with pmf , cml , cnl , or cel / hes . we limited our subjects to cases with pv or et in this study and found 21 appropriate cases in the english literature between 1980 and 2010 [ 115 ] .
the 21 cases in the literature and our 3 cases are shown in table  1 [ 115].table  1cases of renal glomerular disease associated with mpn in the english literaturereferencesagesextypepathological diagnosispathological findingshb ( g / dl)plt ( /l)wbc ( /l)scr ( mg / dl)proteinurea ( g / day)blood pressure ( mmhg)therapyresponse to therapytime course 
 1plomley 47mpvmes22.031000080002.3150/110antihypertensive agent , phlebotomyimproved2plomley 50mpvmes18.8130000012000not documented165/110antihypertensive agent , phlebotomy , busworsened3plomley 45fpvmes22.021500080001.1170/120antihypertensive agent , phlebotomy , busno change4kanauchi 53mpvhspmes cre8.8155000048800not documented150/90phlebotomy , bus , mcnu , psl , mpsl ( pulse ) , cpaworsened2  years5sharma 40fpvfsgsmes20.0410000 
 32000 
 2.0160/100phlebotomyimproved3  years6kasuno 35mpviganmes21.6421000154001.61.6224/140antihypertensive agent , phlebotomy , psl , mpsl(pulse)improved5  years7kasuno 51mpviganmes20.61155000178001.01.0not documentednot documentednot documented4  years8au 48mpvfsgssegmental sclerosis21.3714000120002.5hypertension ( no data)phlebotomy , huworsened20  years9au 63fpvfsgssegmental sclerosis18.71068000114005.4hypertension ( no data)phlebotomy , huworsened10au 25metfsgsmes18.0118000278002.2hypertension ( no data)hu , anti - platelet agentno change11au 39fetfsgssegmental sclerosis10.6954000104005.0hypertension ( no data)huno change12kosch 52mpvfsgstip lesion18.2410000103001.14.0160/90phlebotomyimproved4  years13oymak 66mpvmes epi endo cre20.8660000179007.5not documented160/100phlebotomy , psl , cpaimproved14chun 58mpvmnmn21.821000096100.84.4190/110antihypertensive agent ( acei ) , psl , cpaimproved15chung 46mpviganmes cre21.7258000190002.79.1180/110antihypertensive agent ( acei ) , huimproved16asaba 68metfgnfgn12200001.87.5normal ( no data)antihypertensive agent ( arb ) , psl , mpsl ( pulse)no change28  years17haraguchi 76metfsgsfoamy cell infiltration14.6871000255101.012.7not documentedno treatmentnot documented18saigusa 75metfsgssegmental sclerosis12.7104000098001.09.2146/68huimproved5  years19okuyama 69fpvfsgssegmental sclerosis18.4689000143001.08.3180/88antihypertensive agent , hu , pslimproved3  years20nishi 72fpvmpgnmes11.6781000157800.56.1140/80antihypertensive agent ( arb ) , phlebotomy , hu , anti - platelet agentimproved13  years21ulusoy 56mpvfsgssegmental sclerosis15.2879000115001.96.0160/90antihypertensive agent ( acei ) , phlebotomyimproved22case 176fetiganmes cre15.849000081001.2no data180/90antihypertensive agent ( arb ) , psl , cpaimproved2  years23case 262fetmes11.4978000144000.71.5179/107antihypertensive agent , anti - platelet agentno change24case 351mpviganmes cre15.332600084001.41.2120/73antihypertensive agent ( arb ) , tonsillectomy , pslimproved 
 mes mesangial proliferation , cre crescents formation , igan iga nephropathy , fsgs focal segmenta glomerulosclerosis , mn membranous glomerulonephritis , fgn fibrally glomerulonephritis , mpgn membranous proliferative glomerulonephritis , acei angiotensin - converting enzyme inhibitor , arb angiotensin ii receptor blocker , bus busulfan , mcnu ranimustine , hu hydroxycarbamide , psl prednisolone , mpsl methylprednisolone , cpa cyclophosphamide 
 in units of  /cm ,  it is the text itself 
 time course from onset of mpd to renal biopsy . in 13 cases ,
renal biopsies were performed when mpds were diagnosed almost simultaneously , so spaces are not occupied 
  cases of renal glomerular disease associated with mpn in the english literature 
 mes mesangial proliferation , cre crescents formation , igan iga nephropathy , fsgs focal segmenta glomerulosclerosis , mn membranous glomerulonephritis , fgn fibrally glomerulonephritis , mpgn membranous proliferative glomerulonephritis , acei angiotensin - converting enzyme inhibitor , arb angiotensin ii receptor blocker , bus busulfan , mcnu ranimustine , hu hydroxycarbamide , psl prednisolone , mpsl methylprednisolone , cpa cyclophosphamide 
 in units of  /cm ,  it is the text itself 
 time course from onset of mpd to renal biopsy . in 13 cases ,
renal biopsies were performed when mpds were diagnosed almost simultaneously , so spaces are not occupied the average patient age of these 24 cases ( 16 men and 8 women ) was 55.1  years .
pv was found in 17 patients and et in 7 patients . of the 24 cases , 5 cases , including 2 of ours ,
were diagnosed with iga nephropathy ( igan ) after renal biopsy : focal segmental glomerulosclerosis ( fsgs ) in 10 cases , membranous glomerulonephritis in 1 case , membranoproliferative glomerulonephritis in 1 case , purpura nephritis in 1 case , and fibrillary glomerulonephritis in 1 case .
treatments consisted of antihypertensive drugs for 13 patients , phlebotomy for 12 patients , corticosteroid for 8 patients , hydroxycarbamide for 8 patients , and cyclophosphamide for 4 patients .
urinalysis improvement was seen in 13 cases , 9 of which were treated with antihypertensive agents , 7 with phlebotomy , and 6 with corticosteroid .
although au et al .   detected 5 cases of fsgs ( 3.6  % ) among 138 patients with mpn , the frequency of glomerular disorders among mpn patients is unknown .
therefore , reports that various types of glomerular disease are associated with mpn indicate that the pathogenesis of this condition is complex .
au et al . suggested that high platelet counts and abnormal activation of megakaryocytes are predisposing factors for glomerulosclerosis and that aggressive treatment to lower the platelet count can prevent the development of renal abnormalities . on the other hand , antihypertensive agents , such as an angiotensin ii receptor blocker ( arb ) ,
ulusoy reported the successful treatment of 1 case with antihypertensive drug administration and phlebotomy . a good response after phlebotomy was observed in 2 cases [ 3 , 6 ] .
mpn , especially pv and et , are susceptible to complication by thrombosis or hypertension .
endothelial cell damage could induce activation of platelets and release of cytokines such as pdgf ( platelet - derived growth factor ) .
floege et al .   suggested that pdgf might mediate glomerular injury and cause exacerbation of glomerulonephritis .
other candidate cytokines such as insulin - like growth factor-1 , platelet - activating factor , transforming growth factor- , and plasmalemmal vesicle - associated protein-1 had been reported to play a role in the pathogenesis of glomerulonephritis in mpn patients , though a definite role for these factors has not been established [ 2 , 4 , 5 , 14 ] .
kosch et al .   reported that improvement of hematocrit levels might be useful for reducing protein urea and recovering renal function .
controlling renal hemodynamics and blood cell proliferation might be important for improving renal disease in mpn patients .
unfortunately , with regard to our cases , the effectiveness of these treatments could not be clarified . regarding the clinical course ,
glomerulonephritis was thought to have preceded mpn in 2 of our cases ( cases 2 and 3 ) . in case 1 ,
a case of iga nephropathy , the onset of iga nephropathy did not occur until 2  years after the pv diagnosis . although the documented onset of mpn preceded renal disease in 9 of the 21 previously reported cases , a period of 10  years or more passed between the onset of mpn and that of renal disease in 3 cases , indicating that an association between mpn and the onset of renal disease is unlikely . in those cases ,
, mpn might exacerbate glomerular disease because of the alternation of renal hemodynamics at least in part .
 we performed renal biopsy in three cases complicated by myeloproliferative neoplasms ( mpn ) . 
 although several cases of glomerulonephritis associated with mpn have been reported , the etiologies of the renal disorders were not established ( plomley et al . 
 , aust nz j med , 13:125129 , 1983 ; sharma et al . , 
 nephron , 69:361 , 1995 ; kanauchi et al . , intern med , 33:3640 , 1994 ; kasuno et al . 
 , nephrol dial transplant , 12:212215 , 1997 ; au et al . , am j kid dis , 34:889893 , 1999 ; kosch et al . , 
 nephrol dial transplant , 15:17101711 , 2000 ; oymak et al . , 
 nephron , 86:346347 , 2000 ; chun et al . 
 , am j nephrol , 20:344346 , 2000 ; chung et al . , am j nephrol , 22:397401 , 2002 ; asaba et al . , clin exp nephrol , 7:296300 , 2003 ; haraguchi et al . , clin exp nephrol , 10:7477 , 2006 ; saigusa et al . , j nephrol , 19:656658 , 2006 ; okuyama et al . 
 , clin nephrol , 6:412415 , 2007 ; nishi et al . , clin nephrol , 5:393398 , 2010 ; ulusoy et al . 
 , intern med , 49:2477 , 2010 ) . 
 a review of previous reports of renal biopsy cases with mpn in the english literature suggested that circulation control is important for the treatment of renal disorders that mimic glomerulonephritis in mpn . 
Introduction
Case reports
Case 1
Case 2
Case 3
Discussion