—  SPECIALTY CONFERENCE  —

Renal Pathology

Case 1 - Focal Segmental Glomerulosclerosis, Cellular Variant
Mild Interstitial Fibrosis
Severe Hyaline Arteriolosclerosis
Moderate Arterial Sclerosis

Ginette Lajoie-Starkell
Brampton Memorial Hospital
Brampton, Ontario, Canada





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Clinical History
A previously well 53-year-old Caucasian man was referred from a medical clinic to the emergency department for severe hypertension (systolic blood pressure > 200 mm Hg) and significant pitting edema. In the emergency, investigation revealed haemoglobin of 146 g/L (14.6 g/dL), white blood count of 6.9 X109/L (6.9 x 103/µL), and platelet count of 290 X109/L (290 x 103/µL). The creatinine was 103 µmol/L (1.17 mg/dL), and urea 3.2 mmol/L (8.9 mg/dL), with potassium of 3.7 mmol/L (3.7 mEq/L). Urine dipstick showed 3+ protein and no blood. A CT-scan of the head demonstrated microangiopathic changes, and a chest X-ray showed a widened mediastinum suggestive of malignancy or sarcoidosis. The patient was discharged home with Coversyl 8 mg/daily and hydrochlorothiazide 25 mg daily. A follow-up visit was arranged 4 days later. At that time, the blood pressure was 171/109 mm Hg. Hydrochlorothiazide was discontinued, and he was prescribed Furosemide 20 mg daily. A referral was made to respirology for possible sleep apnea. The family physician saw the patient subsequently. He was initiated on metoprolol 50 mg twice daily, Coversyl 16 mg daily, and Lasix 20mg daily. Additional tests revealed an unchanged creatinine of 106 µmol/L (1.20 mg/dL) with an eGFR of 63 mL/min. The patient was referred to a nephrologist. At the first visit, it was established that the patient's past medical history was limited to a history of smoking discontinued the previous year, and 3 to 4 years history of previously untreated arterial hypertension. Specifically, he had no history of coronary artery disease, cardiac heart failure, diabetes, or stroke. On review, there was no suggestion of systemic symptoms with no rash, arthritis, weight loss, hair loss, oral ulcers, fever, chills, or sweats. He admitted to a history of snoring and daytime fatigue without witnessed apnea. There was no relevant familial history. Examination revealed obesity, blood pressure of 180/110 mm Hg, normal heart sounds with a soft S4. Lasix was increased to 20 mg twice daily, and he was started on Doxazosin 2 mg daily. At a subsequent visit to the nephrologist's office, additional laboratory results were available for review: normal complete blood count, creatinine 103 µmol/L (1.17 mg/dL), fasting blood glucose 6.4 mmol/L (115.3 mg/dL), Hb A1C 0.061 mmol/L (6.1 %), potassium 3.8 mmol/L (3.8 mEq/L), calcium 2.03 mmol/L (8.12 mg/dL), phosphorus 1.04 mmol/L (3.2 mg/dL), albumin 27 g/L (2.7 g/dL), uric acid 464 µmol/L (7.8 mg/mL), total cholesterol 11.38 mmol/L (439.4 mg/dL), normal serum and urine protein electrophoresis, and negative serology for ANA, ds-DNA, rheumatoid factor, HIV, and hepatitis B. Serum complement level was normal (C3 1.60 g/L (160 mg/mL), C4 0.36 g/L (36 mg/mL)). A 24-hour urine collection revealed 14 g protein/day. The patient's serum was positive for Hepatitis C antibodies for which he was referred to a hepatologist by the family physician. On further testing, negative RNA test for Hepatitis C was found indicating previous exposure to the virus but no active infection. A CT-scan of the chest demonstrated extensive mediastinal and hilar adenopathy, with extensive reticulonodular changes throughout the lungs. Antihypertensive medications were adjusted to Micardis 80 mg once daily, Lasix 40 mg twice daily, and Doxazosin 4 mg twice daily. A renal biopsy was considered but deferred until pulmonary issues were clarified. The patient was assessed by respirology and thoracic surgery. A mediastinoscopy and bronchoscopy were completed. The bronchoscopy was normal. Biopsy of the enlarged mediastinal lymph nodes was obtained. The mediastinal lymph node biopsy results supported a presumed clinical diagnosis of sarcoidosis. In view of the lung parenchymal involvement, normal calcemia, and absence of significant symptoms, no specific treatment was recommended for sarcoidosis. A renal biopsy was performed, 6 months after the initial presentation.


Case 1 - Figure 1
A glomerulus with a partly sclerotic segmental lesion. There is also segmental endocapillary hypercellularity with karyorrhexis. Hypertrophied podocytes are seen around the lesion. (Original magnification= x200, PAS)
Case 1 - Figure 2
The segmental sclerotic lesion in this glomerulus is expanded, and contains foam cells. The lesion is surrounded by a small rim of slightly enlarged glomerular visceral epithelial cells. (Original magnification= x200, H&E)
Case 1 - Figure 3
Focal segmental sclerosis, NOS (Original magnification= x200,PAS)
Case 1 - Figure 4
Numerous protein reabsorption droplets in the cytoplasm of tubular epithelial cells. (Original magnification= x400, PAS)

Case 1 - Figure 5
By immunofluorescence, there is complete absence of glomerular staining for IgG. (Original magnification= x400).
Case 1 - Figure 6
Immunofluorescence demonstrates non-specific trapping of C3 in a segmental sclerotic lesion. (Original magnification= x200)
Case 1 - Figure 7
Albumin cytoplasmic droplets in the cytoplasm of tubular epithelial cells by immunofluorescence . (Original magnification= x400)
Case 1 - Figure 8
Electron microscopy photomicrograph of a few glomerular capillaries exhibiting complete effacement of foot processes. Large reabsorption droplets are seen in the cytoplasm of the glomerular visceral epithelial cells (right lower corner). (Original magnification= x2500)

Case 1 - Figure 9
A glomerulus with segmental endocapillary hypercellularity containing mild exudation, and extensive karyorrhexis. The cellular lesion is partly surrounded by large glomerular visceral epithelial cells that contain cytoplasmic protein droplets. (Original magnification= x200, H&E)
Case 1 - Figure 10
Segmental endocapillary hypercellularity with karyorrhexis. The lesion is capped by prominent glomerular visceral epithelial cells. (Original magnification= x200, HPS)


Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:

Light Microscopy:
A single core of renal tissue from the cortico-medullary junction contains 21 glomeruli of which 15% are globally sclerosed. The remaining glomeruli appear enlarged (glomerulomegaly). Fifteen percent of glomeruli exhibit peripheral segmental scars of various sizes associated with capsular adhesions. In another 10% of glomeruli, segmental lesions demonstrating endocapillary hypercellularity are seen that contain apoptotic cells and karyorrhexis. Some of these lesions are surrounded by hyperplastic and hypertrophied glomerular visceral epithelial cells. In the non-affected segments, there is no increase in mesangial matrix and no mesangial hypercellularity. The glomerular basement membranes appear to be within normal limits on PAS stain, with no areas of collapse. Mild interstitial fibrosis and tubular atrophy involving approximately 15% of the cortical surface is observed. There was no interstitial inflammation and no granulomas. Moderate arterial sclerosis and severe hyaline arteriolosclerosis are present.

Immunofluorescence Microscopy:
Up to 12 glomeruli were present in one core of renal cortex with no globally sclerosed glomeruli. There is no glomerular staining for IgG, IgA, IgM, kappa, lambda, C4, C1q, fibrinogen, and albumin. C3 is noted in a sclerosed glomerular segment. Cytoplasmic droplets of IgG and IgA are seen in glomerular visceral epithelial cells. Tubular epithelial cells contain numerous cytoplasmic droplets of albumin. Positive and negative controls stained appropriately.

Electron Microscopy:
Three glomeruli are examined ultrastructurally. One glomerulus exhibits a segmental scar. The mesangium is not expanded. There are no electron-dense immune-type deposits. The glomerular basement membranes are within normal limits with no thinning, thickening, and/or lamellation. There is complete effacement of foot processes in all three glomeruli. There are no tubulo-reticular inclusions in the cytoplasm of glomerular capillary endothelial cells.

Differential Diagnoses:
By light microscopy, the glomerular lesions are focal and segmental with a mix of cellular lesions and segmental scars. Thus, the main differential diagnosis includes entities that fall under the wide category of primary and secondary focal segmental glomerulosclerosis. In this particular case, the specific diseases to be considered are primary focal segmental glomerulosclerosis (FSGS), focal and segmental endocapillary proliferative glomerulonephritis, and focal and segmental pauci-immune necrotizing glomerulonephritis (ANCA-associated or not). The latter two entities can result in segmental sclerotic lesions as a result of a non-specific response to injury. The absence of immune complexes, as demonstrated by immunofluorescence and electron microscopy, rules out a diagnosis of immune complex-mediated endocapillary glomerulonephritis, such as lupus nephritis. Nephrotic syndrome is a not infrequent mode of clinical presentation in patients with focal and segmental endocapillary glomerulonephritis although it is usually seen alongside nephritic symptoms which were not present in this patient. Furthermore, there is complete absence of systemic symptoms, and the patient's serology is negative for ANA. To consider a diagnosis of pauci-immune necrotizing glomerulonephritis, one would need convincing necrotizing lesions, fibrinoid necrosis and/or crescents, none of which are present. Furthermore, clinically, the presentation is that of a nephrotic syndrome with no systemic symptoms. Patients with glomerular scars due to pauci-immune glomerulonephritis can present with nephrotic range proteinuria that is usually less than 14 g/day but not typically with a nephrotic syndrome. Red blood cells and red blood cell casts were not reported in the urine. Finally, serology for ANCA, albeit obtained after initiation of treatment, was negative. The findings of focal and segmental glomerular scars, negative immunofluorescence, and complete effacement of foot processes by electron microscopy taken together with the clinical presentation of nephrotic syndrome (classic triad of nephrotic range proteinuria, hypoalbuminemia, and peripheral edema) fit nicely with a diagnosis of FSGS. Ultrastructural changes of the glomerular basement membrane typical of Alport syndrome are absent. Classification of focal segmental glomerulosclerosis Focal segmental glomerulosclerosis is a descriptive term that encompasses a variety of entities, all with different pathogenetic mechanisms. A collaborative effort was made to separate the various morphological variants of FSGS into 5 distinct and mutually exclusive variants, resulting into the Columbia Classification [1]. Alternatively, persuading arguments have been made to classify FSGS into various podocytopathies based on the pathogenetic mechanisms and genetic pathways [2, 3, 4, 5] allowing for a more targeted and tailored therapy. Ideally, the different methods of classifying FSGS will have relevance to each other, and will not be mutually exclusive. The Columbia Classification is not without controversy or limitations. Interobserver variability has not been tested but is likely to be significant [6]. Furthermore, it is worth noting that there is overlap of some features in each category. For example, segmental cellular lesions can be seen in the tip, collapsing, and cellular variants [1, 7], and hyperplasia and hypertrophy of glomerular visceral epithelial cells can be observed in all cases of FSGS, except perihilar focal segmental glomerulosclerosis [1]. Sample size is another variable that could significantly impair our ability to detect diagnostic lesions, resulting in misclassification [7, 8]. Furthermore, glomerular lesions of FSGS appear to evolve over time in some, if not many, patients [8]. Nevertheless, in every day practice, the Columbia Classification is the most clinically useful tool for the diagnosis and treatment of FSGS [9]. For the case under discussion, according to the diagnostic hierarchy offered by The Columbia Classification , one would have to consider, in order, a diagnosis of collapsing variant, tip variant (exclude perihilar lesions), cellular variant, perihilar FSGS, and FSGS not otherwise specified (NOS). The diagnosis of collapsing variant is based on the finding of "at least 1 glomerulus with collapse and overlying podocyte hypertrophy and hyperplasia" [1]. All the lesions identified were expansile as opposed to collapsed, and tended to fill the Bowman's space. Furthermore, the clinical presentation of an older Caucasian male with relatively well preserved renal function is not typical for the collapsing variant of FSGS [7]. Localization of the cellular lesion "at the tip domain, with either adhesion between the tuft and Bowman's capsule at the tubular lumen or neck, or confluence of podocytes with parietal or tubular epithelial cells at the tubular lumen or neck" [1] would classify this case as a tip lesion whether the lesion has a cellular appearance or not. None of the cellular lesions were specifically identified at the tubular pole in this well-sampled biopsy. Thus, the case fits into the definition of the Columbia Classification for cellular FSGS which specifically requires "at least 1 glomerulus with endocapillary hypercellularity involving at least 25% of the tuft and causing occlusion of the capillary lumen/lumina" [1].

Final Diagnosis:
Focal segmental glomerulosclerosis, cellular variant Mild interstitial fibrosis Severe hyaline arteriolosclerosis Moderate arterial sclerosis

Case Discussion:
The cellular variant of FSGS is the least common variant in most series of cases of idiopathic FSGS, ranging from 0% to 4.6% in adults [6, 7, 10]. It follows that it is the least studied variant. It has been pointed out that the cellular lesion was previously described in the literature [1], but it was not until 1985 that Schwartz and Lewis [11] coined the term "cellular lesion" for that variant of FSGS. That group also later reported a series of cases that appears to include both collapsing and cellular lesions [12]. In the subsequent Columbia Classification, the cellular variant of FSGS was separated and distinguished from the collapsing variant. Although it remains a controversial entity, the fact that cellular FSGS recurs in kidney transplants as a cellular variant has been interpreted as further evidence of its existence as a stand-alone variant [8].

Only one study exists in which the cellular variant of FSGS, as defined in the Columbia classification, was further characterized clinically and pathologically, and compared to other variants [7]. In general, patients with cellular FSGS were similar to those with the tip variant. The patients were older (mean= 48.8 years) with no predilection for African-Americans as opposed to patients with collapsing FSGS. The time to biopsy was shorter than for most other variants (4.3 months) except for the tip variant (2.1 months). Most patients presented with the full nephrotic syndrome (86.4%) with a mean serum albumin of 2.1 g/dL. In many patients, the presentation was sudden or even explosive. Approximately one half of patients suffered from renal insufficiency at the time of presentation.

Pathologically, the biopsies diagnosed as cellular contained the lowest average of glomeruli (14.6 glomeruli), with a mean of 13.6% globally sclerosed glomeruli. By definition, at least one cellular lesion was present, and cases with collapsing features or tip lesions were excluded. The cellular lesions tended to be small, involving from 25% to 50% of the glomerular tuft, and contained either foam cells or mononuclear cells/neutrophils with pyknosis or karyorrhexis but no fibrinoid necrosis. Similar to the case presented here, significant effacement of foot processes (90-100%) was noted in the large majority of cases by ultrastructural examination. Mild to moderate visceral epithelial cell hypertrophy and hyperplasia was seen in all cases, overlying at least one cellular lesion.

After treatment, approximately 1/3 of patients experienced either complete or partial remission of the nephrotic syndrome, and another 1/3 progressed to end-stage renal disease. That response was intermediate between that of collapsing FSGS (worse renal prognosis) and tip variant (best prognosis). The authors admitted that unsampled cases of collapsing FSGS or tip variant could have been included in their series, given the fact that the cases diagnosed as cellular FSGS had the least average number of glomeruli per case.

The authors caution for the need for sufficient glomerular sampling and careful exclusion of both tip and collapsing variants in making a diagnosis of cellular FSGS, using deeper sections if necessary. Indeed, in their study, with deeper sectioning, some cases were assigned a diagnosis of collapsing FSGS, and approximately 1/3 of cases were found to be under sampled tip variant. The authors suggest that the cellular variant of FSGS might represent an advanced stage of tip variant, even in cases where the tip lesion cannot be recognized any longer. Against this argument is the fact that cellular FSGS appears to share a pathway of dysregulated podocyte with idiopathic and HIV-related collapsing FSGS [13]. However, the exact pathogenetic mechanisms underlying cellular FSGS have not been completely elucidated.

Finally, one must strive to exclude secondary causes in every case before concluding that one is dealing with a primary or idiopathic FSGS. Each variant defined by the Columbia Classification is linked to different secondary causes (Table 1). That list is expanding rapidly, but no specific secondary cause has yet been linked to the cellular variant.



Table 1. Non-exhaustive list of secondary causes of focal segmental glomerulosclerosis*

FSGS Variants Secondary causes
Collapsing HIV, Parvovirus B-19, heroin, pamidronate, familial/hereditary, anabolic steroids, interferon therapy
Tip Lesion Heavy proteinuria
Cellular None known (exclude tip lesion)
Perihilar Obesity, reflux nephropathy, compensatory hypertrophy, prematurity and low birth weight, anabolic steroids
Not otherwise specified (NOS) Idiopathic or advanced stage of above variants

*Modified from reference 9

Is sarcoidosis a likely secondary cause of FSGS in this patient?

Renal involvement in patients with sarcoidosis is infrequent, affecting from 4% to 20% of patients, and usually remains subclinical [14, 15]. When present, renal disease includes granulomatous and non-granulomatous tubulo-interstitial nephritis, secondary obstructive uropathy, signs and symptoms related to hypercalcemia (calciuria, nephrocalcinosis, and nephrolithiasis), and progressive interstitial fibrosis [14, 15]. Glomerular disease is rare and may be coincidental. The reported glomerular diseases include a large predominance of membranous glomerulopathy. Isolated case reports of IgA glomerulopathy, acute post-infectious glomerulonephritis, amyloidosis, membranoproliferative glomerulopathy, minimal change nephrotic syndrome, mesangioproliferative glomerulonephritis with IgM deposits, crescentic glomerulonephritis, and ANCA-associated glomerulonephritis also exist [14, 15, 16, 17, 18]. Excluding the present case, only 6 cases of FSGS have been reported in the English literature so far [19, 20, 21, 22, 23, 24] (Table 2). Earlier reports of FSGS-like lesions that lacked immunofluorescence studies are not included [25, 26].

The relationship between sarcoidosis and glomerular disease, if it exists, remains unclear. Arguing against a causal relationship is the rarity of reports, and the large variety of reported glomerular diseases, not pathogenetically linked to each other. However, the close temporal relationship of renal presentation with the diagnosis of sarcoidosis in most patients with FSGS is intriguing (Table 2). Six out of seven patients presented with proteinuria within one year of diagnosis of sarcoidosis, and half of these patients received a simultaneous diagnosis of sarcoidosis and FSGS. The patients ranged in age from 26 to 58 years (mean=37), with an equal gender distribution. Most had radiological stage II sarcoidosis (adenopathy and reticulonodular involvement of the lung). All but one patient received corticosteroid treatment for sarcoidosis. Most patients were hypertensive at the time of renal presentation, with a mean level of proteinuria of 11.45 g/d (range: 4.5 to 29.4 g/d). Since all cases were reported before 2004, a subset of FSGS was not given except for the present case. In all reports, the FSGS variant cannot be determined with certainty from the description and illustrations. A patient with artery stenosis secondary to sarcoidosis died of causes unrelated to the renal disease. Of the six remaining patients, five received prednisone. One third of patients progressed to renal failure, and underwent kidney transplantation with good results. Another third remained stable, and 2 patients experienced either a remission or significant decrease in proteinuria. In one instance only, the pathogenesis of FSGS is likely related to renal artery stenosis and arterial hypertension [20] but is undetermined in all other cases.

Sarcoidosis is a multisystem disorder of unknown etiology characterized by the formation of non-caseating granulomas containing activated T-cells (mostly CD4 T-helper cells) and macrophages. Both types of cells release numerous chemokines and cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-12, and interleukin-18 among others) [17]. Conceivably, a T-cell derived permeability factor may play a role in the development of focal segmental glomerulosclerosis in patients with sarcoidosis [21, 22, 23, 24].

In summary, the link between sarcoidosis and glomerular disease, and FSGS in particular, has not been proven. Until we better understand the pathogenesis of both conditions, and prove the existence of a common link, we cannot exclude that the two diseases happen coincidentally.

In conclusion, as our knowledge of pathogenetic mechanisms of FSGS increases, the hope is that classification will be based on the type of podocytopathy as opposed to the resulting morphological expression (although the two are likely to be linked to some degree) in a way that would be practical to achieve in most laboratories, resulting in a tailored therapeutic approach for individual patients.

Clinical Follow-Up
The patient was initiated on therapy with oral prednisone 80 mg daily. Two months after initiation of therapy, urinary protein excretion decreased from 14 grams to 4 grams daily but serum creatinine has increased slightly, from 103 µmol/L (1.17 mg/dL) to 120 µmol/L (1.36 mg/dL).

Table 2. Sarcoidosis and focal segmental glomerulosclerosis

Case Age Sex Race Sarcodoisis (Radiological stage) Tx of sarcoid Proteinuria in relationship to diagnosis of sarcoidosis Hypertension with renal presentation Proteinuria (g/d) Creatinine (mg/dL) FSGS Variant Tx Follow-up Presumed pathogenesis
Lee et al [19] 26 M Unknown Adenopathy + lung Steroids Synchronous Yes 8.0 1.0 Not reported.Query perihilar Steroids + cyclopphospha-mide Stable at 18 mos
Godin et al [20] 40 M Unknown Adenopathy + lung Prednisone 1 year post Yes 4.5 N/A Not reported Decompression of renal artery stenosis Patient died of unrelated causes Arterial hypertension
Hakaim et al [21] 28 F African american Adenopathy + lung Prednisone 1 year post Not reported Not reported 2.0 Not reported Not reported Renal transplant. Stable at 25 months post-transplant T-cell dysfunction
Peces et al [22] 31 M Unknown Adenopathy + lung Prednisone Synchronous No 8.3 1.03 Not reported Prednisone Resolution of proteinuria at 5 months, and adenopathy at 9 months T-cell dysfunction and cytokines
Veronese et al [23] 29 F African american Adenopathy + lung Prednisone 2 months post Unknown 29.4 3.4 Not reported Prednisone Renal transplant. Stable at 18 months post-transplant T-cell dysfunction and cytokines
Altiparmak et al [24] 58 F Not known Adenopathy + lung, inactive at time of renal disease Steroids 23 years post Yes 4.5 1.37 Not reported ACE inhibitor Stable at 12 months. Slight decrease in proteinuria (3.1 g/d) T-cell dysfunction
Present case (USCAP 2011) 53 M Caucasian Adenopathy and lung None Synchronous Yes 14.0 1.17 Cellular Prednisone and ACE inhibitor Decreased proteinuria (4.0 g/day). Creatinine 1.35 mg/dL Unknown

Conclusion(s):
In conclusion, as our knowledge of pathogenetic mechanisms of FSGS increases, the hope is that classification will be based on the type of podocytopathy as opposed to the resulting morphological expression (although the two are likely to be linked to some degree) in a way that would be practical to achieve in most laboratories, resulting in a tailored therapeutic approach for individual patients.

References:
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  2. Nair R: Focal segmental glomerulosclerosis: Cellular variant and beyond. Kidney Int 2006;70:1676-1678

  3. Barisoni L, Schnaper HW, Kopp JB: Advances in the biology and genetics of the podocytopathies. Arch Pathol Lab Med 2009;133:201-216

  4. Thomas DB: Focal segmental glomerulosclerosis: A morphologic diagnosis in evolution. Arch Pathol Lab Med 2009;133:217-223

  5. Yang H-C, Fogo AB: 'Idiopathic' FSGS: an increasingly obsolete diagnosis? Nephrol Dial Transpl 2010;25:654-656

  6. Deegens JKJ, Steenbergen EJ, Borm GF, Wetzels JFM: Pathological variants of focal segmental glomerulosclerosis in an adult Dutch population-epidemiology and outcome. Nephrol Dial Transpl 2008;23:186-192

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  8. Ijpelaar DHT, Farris AB, Goemaere N, et al: Fidelity and evolution of recurrent FSGS in renal allografts. J Am Soc Nephrol 2008;19:2219-2224

  9. D'Agati VD: The spectrum of focal segmental glomerulosclerosis: new insights. Curr Opin Nephrol Hypertens 2008;17:271-281.

  10. Thomas DB, Franceschini N, Hogan SL, et al: Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 2006;69:920-926

  11. Schwartz MM, Lewis EJ: Focal segmental glomerular sclerosis: the cellular lesion. Kidney Int 1985;28:968-974

  12. Schwartz MM, Evans J, Bain R, Korbet SM: Focal segmental glomerulosclerosis: prognostic implications of the cellular lesion. J Am Soc Nephrol 1999;10:1900-1907

  13. Shankland SJ, Eitner F, Hudkins KL, et al: Differential expression of cyclin-dependent kinase inhibitors in human glomerular disease: role in podocyte proliferation and maturation. Kidney Int 2000;58:674-683

  14. Göbel U, Kettritz R, Schneider W, Luft FC: The protean face of renal sarcoidosis. J Am Soc Nephrol 2001;12:616-623

  15. Dahl K, Canetta PA, D'Agati VD, Radhakrishnan J: A 56-year-old woman with sarcoidosis and acute renal failure. Kidney Int 2008;74817-821

  16. Michaels S, Sabnis SG, Oliver JD, Guccion JG: Renal sarcoidosis with superimposed postinfectious glomerulonephritis presenting as acute renal failure. Am J Kidney Dis 2000;36:E4

  17. Morita H, Yoshimura A: Glomerulonephritis in sarcoidosis. Clin Exp Nephrol 2006:10:85-86

  18. Kanamori H, Ota M, Takeoka H, et al: IgM-immune complex glomerulonephritis associated with sarcoidosis. Clin Exp Nephrol 2006;10-68-73

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  20. Godin M, Fillastre J-P, Ducastelle Y, Hemet J, Morere P, Nouvet G: Sarcoidosis, retroperitoneal fibrosis, renal arterial involvement, and unilateral focal glomerulosclerosis. Arch Intern Med 1980;140:1240-1242

  21. Hakaim AG, Stilmant MM, Kauffman J, et al: Successful renal transplantation in a patient with systemic sarcoidosis and renal failure due to focal glomerulosclerosis. Am J Kidney Dis 1992;19:493-495

  22. Peces R, de la Torre M, Sanchez-Fructuoso A, Escalada P: Focal segmental glomerulosclerosis associated with pulmonary sarcoidosis. Nephron 1993;65:656-657

  23. Veronese FJV, de Azevedo Henn L, Faccin CS, et al: Pulmonary sarcoidosis and focal segmental glomerulosclerosis: case report and renal transplant follow-up. Nephrol Dial Transplant 1998;13:493-495

  24. Altiparmak MR, Oygar D, Bilir M, Kiliçarslan I, Serdengeçti K: A rare cause of focal segmental glomerulosclerosis: Sarcoidosis. Nephron 2002;90:211-212

  25. Teilum G: Glomerular lesions of the kidneys in sarcoidosis (Boeck's sarcoid). Acta Pathol Microbiol Scand 1951;28:294-301

  26. McCoy RC, Tisher CC: Glomerulonephritis associated with sarcoidosis. Am J Pathol 1972;68:339-358