Cystic Diseases of the        Kidney                                  CNE      Ahmed Hassan Mohamed MD                   L...
Kidney cysts Cysts are abnormal blisters that may contain fluid or other  matter. Many kinds of cysts can affect the kidn...
Categories Developmental: Multicystic dysplastic kidney disease Genetic:ARPKD, ADPKD, juvenile nephronophthisis  (JNPHP)...
Bonsib (2009) classification of renal cysticdiseases & congenital anomalies of the kidney &urinary tract.ESNT-CNE 1st Cour...
Bosniak Classification of Renal Cysts    Class I: Simple benign cysts with a well-defined     homogeneous mass, a thin wa...
Pathophysiology      Cysts develop from renal tubule segments and most     detach from the parent tubule after they grow ...
Pathophysiology MCDK represents abnormal development 2ndry to                         1-dysfunctional genetics    2-abnor...
Polycystin 1 involved in cell-cell interaction, activates JAK-STATpathway, causing cell cycle arrest.Polycystin 2 involves...
Pathophysiology    ARPKD is due to mutations in PKHD1, a gene that         encodes fibrocystin / polyductin, which plays ...
Pathophysiology Medullary sponge kidney of unknown etiology (?  AD/ sporadic mutation). there is a cystic dilatation of  ...
Kidney cystsESNT-CNE 1st Course Cairo Sept 10-14, 2012
Cut surface of a nephrectomy       specimen from a patient with a Medullary cysts in normal size         multicystic dyspl...
Nephrectomy specimen from                       External surface of a nephrectomya patient with a large benign            ...
Epidemiology MCDK 1:1000-4000 live births. (>male). ADPKD 1:400-1000 , has a bimodal distribution of  onset (more rapid ...
Epidemiology MSK 1:5000 (M: F 2:1), is found in 20% of pts with  nephrolithiasis. In acquired cystic renal disease (> in...
Clinically ADPKD presents flank pain ,hematuria, proteinuria,  UTI, HTN, calculus & renal insufficiency (it is intact  un...
Clinically                                   Cardiac disease includes:                                                   ...
ARPKD clinical presentation   four presentations:     Neonatal & infancy with a profound respiratory      compromising 2...
Clinically       MCKD (insidious onset, > older pts associated with                         hyperuricemia & gouty arthrit...
Clinically  MSK, (3rd and 5th decades of life), usually   a symptomatic /incidental (0.5% in pts examined  with excretory...
Clinically TSC, presented by:   Triad of adenoma sebeceum, epilepsy & MR   Formation of angiomyolipomas (50-70%) of ski...
Differential diagnosis of different types ofrenal cystsDisease                           Kidney size   Cyst size   Cyst lo...
Morbidity & Mortality   Cystic renal disease accounts for 10% of ESRD pts.             ADPKD account for 5-10% of ESRD p...
Diagnosis of cystic kidney disease Physical examination: to detect high blood pressure  or enlarged kidneys Urine tests:...
CT abdomen demonstratesA prenatal sonogram of a fetus with           bilateral atrophic kidneys witha multicystic dysplast...
CT abdomen reveals the kidneysCT abdomen demonstrates multiple             are bilaterally enlarged with multiplehepatic c...
Axial non enhanced CT scan of a 1-day-old boy with ARPKD shows   massively enlarged, hypo attenuating kidneys (K) that occ...
Contrast urography shows normal                Unenhanced CT scan of abdomencollecting system and renal pelvis            ...
A right-sided abdominal mass, which            Bilateral renal angiomyo-lipomasis a renal cell carcinoma in a case of     ...
Contrast-enhanced axial CT scan abdomen shows cysts within thepancreas and the right kidney. Note also a solid 3 cm lesion...
Treatment MCDK is not treatable. Regular follow up of infant for the first few years by  ultrasounds Nephrectomy of unh...
Treatment ADPKD, Treatment may include: Blood pressure control (ACEI,ARB). MTOR inhibitors show some benefit in limitin...
Treatment Treatment of urinary UTI Cysts that are painful, infected, bleeding, or causing a  blockage may need to be dra...
HALT PKD is the first large multicenter randamized double blindplacebo control study that evaluate potential benefits of r...
Treatment              MCKD, there is no cure for this disease.                              Drinking plenty of fluids a...
Treatment    MSK , to reduce the incidence of stones formation in     high risk patients. They can include the following:...
Treatment of VHL VEGF inhibitors, sorafenib and sunitinib FDA  approval. Rapamycin may also be an option. Bevacizumab, ...
Treatment of TSC    ? Rapamycin decrease the size of mass of     angiomyolipomas by 50% ( as it is associated with     ph...
ESNT-CNE 1st Course Cairo Sept 10-14, 2012
References1-Amoroso. Autosomal dominant medullary cystic kidney disease with or without   hyperuricemia. Orphanet. June 20...
References8-Guay-Woodford LM. Renal cystic diseases: diverse phenotypes converge on the   cilium/centrosome complex. Pedia...
Important abbreviationAC= adenyl cyclaseAMP= adenosine mono phosphateATP= adenosine triphosphateCDK= Cyclin dependant kina...
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Cystic kidney diseases dr.a.hassan end123

  1. 1. Cystic Diseases of the Kidney CNE Ahmed Hassan Mohamed MD Lecturer of nephrology National institute urology & nephrology NIUNESNT-CNE 1st Course, Cairo, Sept 10-14, 2012
  2. 2. Kidney cysts Cysts are abnormal blisters that may contain fluid or other matter. Many kinds of cysts can affect the kidney. Kidney cysts are classified by: Cause – inherited, acquired kidney disease or advancing age Features – like the number of cysts (one or more) and whether the cysts are simple or complicated. Location – outer (cortex) or inner (medulla) part of the kidney ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  3. 3. Categories Developmental: Multicystic dysplastic kidney disease Genetic:ARPKD, ADPKD, juvenile nephronophthisis (JNPHP), medullary cystic kidney disease (MCKD), glomerulocystic kidney disease (GCKD) . Cysts associated with systemic disease: Von Hippel- Lindau syndrome, tuberous sclerosis complex. Acquired - Simple cysts, acquired cystic renal disease, medullary sponge kidney. Malignancy: cystic renal cell carcinoma (RCC).ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  4. 4. Bonsib (2009) classification of renal cysticdiseases & congenital anomalies of the kidney &urinary tract.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  5. 5. Bosniak Classification of Renal Cysts Class I: Simple benign cysts with a well-defined homogeneous mass, a thin wall. These lesions do not enhance. Class II: Minimally complicated cysts with smooth thin internal deputations, thin peripheral rim of calcification in its wall or septa. These lesions do not show enhancement Class IIF: Minimally complicated cysts, ?hyper dense, contain more calcium in the wall & may have thicker internal deputations. Follow up scanning is needed. Class III: More complicated cystic structures with irregular thickened septa, wall thickening, solid non-enhancing mural nodules, or irregular calcifications. Surgical exploration. Class IV: Malignant cyst, with non-uniform wall thickening, have irregular margins, and/or contain solid components that enhance on CT (total nephrectomy is warranted).ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  6. 6. Pathophysiology  Cysts develop from renal tubule segments and most detach from the parent tubule after they grow to a few millimeters in size.  Cyst development is generally attributed to  Increased proliferation of tubular epithelium  Abnormalities in tubular cilia  Excessive fluid secretionESNT-CNE 1st Course Cairo Sept 10-14, 2012
  7. 7. Pathophysiology MCDK represents abnormal development 2ndry to 1-dysfunctional genetics 2-abnormal differentiation of the metanephros  ADPKD is due to mutations in the genes PKD1(Chromosome 16) & PKD2(chromosome 4) that encode polycystin proteins.  Mutated PKD1 and PKD2 genes cause the production of polycystin-1 and polycystin-2 proteins respectively. ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  8. 8. Polycystin 1 involved in cell-cell interaction, activates JAK-STATpathway, causing cell cycle arrest.Polycystin 2 involves calcium signaling via G protein. Expressed in.renal tubular epithelium, hepatic ducts & pancreatic ductsESNT-CNE 1st Course Cairo Sept 10-14, 2012
  9. 9. Pathophysiology ARPKD is due to mutations in PKHD1, a gene that  encodes fibrocystin / polyductin, which plays critical roles in collecting-tubule and biliary development.  JNPHP: (AR inheritance). MCKD: (AD), there are 2 types:  MCKD1 due to mutations in the MCKD1 gene (average age of ESRD 62YRS)  MCKD2 is caused by mutations in the UMOD gene (on chromosome 16 & encodes uromodulin. ((average age of ESRD 32yrs).ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  10. 10. Pathophysiology Medullary sponge kidney of unknown etiology (? AD/ sporadic mutation). there is a cystic dilatation of the collecting tubules in 1 or more renal pyramid. VHLS: due to mutations in the VHL gene on (ch. 3), TS: due to by mutations in the suppressor genes TSC1 (ch. 9) & TSC2 (ch. 6), which encode hamartin and tuberin, respectively. Acquired Cystic Kidney Disease d.t. an unidentified waste product not removed through dialysisESNT-CNE 1st Course Cairo Sept 10-14, 2012
  11. 11. Kidney cystsESNT-CNE 1st Course Cairo Sept 10-14, 2012
  12. 12. Cut surface of a nephrectomy specimen from a patient with a Medullary cysts in normal size multicystic dysplastic kidney kidney in a case of (MCDK). nephronophthisisESNT-CNE 1st Course Cairo Sept 10-14, 2012
  13. 13. Nephrectomy specimen from External surface of a nephrectomya patient with a large benign specimen from a patient withsimple cyst. autosomal dominant polycystic kidney disease (ADPKD). ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  14. 14. Epidemiology MCDK 1:1000-4000 live births. (>male). ADPKD 1:400-1000 , has a bimodal distribution of onset (more rapid in male). ARPKD 1:6000-55,000 live births, with a heterozygous carrier frequency of 1 per 70 JNPHP affects 1:5000 persons. JNPHP & MCKD 10-20% of children with CRF. TS 1:10,000-50,000 (25% of pts have renal cysts). VHLS 1:39,000, (M=F) & 2/3 pts develop renal cysts, & presents in the 3rd or 4th decade of lifeESNT-CNE 1st Course Cairo Sept 10-14, 2012
  15. 15. Epidemiology MSK 1:5000 (M: F 2:1), is found in 20% of pts with nephrolithiasis. In acquired cystic renal disease (> in male) , cysts are present in 8-13% of pts with CRF prior to dialysis, 40-60% > 5 yrs of dialysis & > 90% >10 yrs. Simple cysts (5% of the general population & rare in children), are the most common cystic renal lesions, account for 65-70% of renal masses & are present in 25-33% of pts > 50 yrs. Cystic RCC accounts for < 1% of RCC cases.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  16. 16. Clinically ADPKD presents flank pain ,hematuria, proteinuria, UTI, HTN, calculus & renal insufficiency (it is intact until the 4th decade & decline at a rate of 4-6ml /min/yr). (faster in PKD1, proteinuria, HTN, male) Extra renal manifestations includes:  cerebral aneurysms (4% based on F.H., age & SAH increases risk).  Hepatic cysts (80%), age (15-40 yrs), (>female) , multiple pregnancies (? Estrogen) & mostly a symptomatic.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  17. 17. Clinically Cardiac disease includes:   MVP & AR 30%  Coronary aneurysm not infrequent  Asymptomatic pericardial effusion represents 30%.  Colonic diverticula  abdominal pain  Abdominal wall hernia (45% of pts).ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  18. 18. ARPKD clinical presentation four presentations:  Neonatal & infancy with a profound respiratory compromising 2ndry to oligohydraminas.  Childhood & adolescence with hepatic disease predominant.  Cholongitis  ESRD ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  19. 19. Clinically  MCKD (insidious onset, > older pts associated with hyperuricemia & gouty arthritis)  JNPHP) young children, associated with retinitis pigmentosa, hepatic fibrosis & situs inversus), both presented by: polyuria (the earliest sign), polydepsia from urinary  concentration defect.  Nocturia, Weakness &? normal blood pressure in early stages of renal dysfunction due to renal salt wasting.  Late in the disease, manifestation of CRF may develop.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  20. 20. Clinically MSK, (3rd and 5th decades of life), usually a symptomatic /incidental (0.5% in pts examined with excretory urography).  Recurrent ca phosphate , ca oxalate stones  U.T.I / Haematuria VHLS: commonest systemic lesion is hemangio- blastoma of eye & brain + pheochromocytoma (10- 20%) + renal involvement, multiple cysts, RCC (bilateral, multicenteric & affect 2/3 Pts).ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  21. 21. Clinically TSC, presented by:  Triad of adenoma sebeceum, epilepsy & MR  Formation of angiomyolipomas (50-70%) of skin, kidneys, brain & other organs  Benign cysts (30-50%) & RCC (2%). Condition ? asymptomatic or flank pain, hematuria from mass effect of angiomyolipomas & cysts together with HTN (renin dependant) manifestation.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  22. 22. Differential diagnosis of different types ofrenal cystsDisease Kidney size Cyst size Cyst location LiverNephronophthisis Small 1MM-2CM Medullary NormalAcquired cyst Normal/small 0.5-3CM Any NormalMedullary sponge Normal / MM Precalyceal Normal EnlargedARPKD Enlarged MM Any FibrosisMulticystic Enlarged 1MM-10CM Any NormaldysplasticADPKD Enlarged MM-10CM Any Cysts ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  23. 23. Morbidity & Mortality Cystic renal disease accounts for 10% of ESRD pts.  ADPKD account for 5-10% of ESRD pts.  ARPKD accounts for 5% of ESRD in children, with neonatal mortality (25-35%)& > 50% of pts with ARPKD require kidney transplant before age 20 yrs. JNPHP is the most common cause of genetic ESRD in children. Patients with acquired cystic disease are more likely to develop RCC (5-25%), which are commonly bilateral & 15% are metastatic.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  24. 24. Diagnosis of cystic kidney disease Physical examination: to detect high blood pressure or enlarged kidneys Urine tests: for hematuria &/or proteinuria /infection Blood tests: to assess kidney function/CBC Renal U/S: It is good at identifying even quite small cysts Computed tomography (CT) and magnetic resonance imaging (MRI) scans can detect very small cysts. Excretory urography. Genetic testing – not a routine test.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  25. 25. CT abdomen demonstratesA prenatal sonogram of a fetus with bilateral atrophic kidneys witha multicystic dysplastic kidney. multiple renal cysts in a dialysis patient. ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  26. 26. CT abdomen reveals the kidneysCT abdomen demonstrates multiple are bilaterally enlarged with multiplehepatic cysts in a case of ADPKD cysts in a case of ADPKD.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  27. 27. Axial non enhanced CT scan of a 1-day-old boy with ARPKD shows massively enlarged, hypo attenuating kidneys (K) that occupy most of the abdominal area.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  28. 28. Contrast urography shows normal Unenhanced CT scan of abdomencollecting system and renal pelvis with medullary nephrocalcinosiswith striated and saccular collections in pt. with medullary spongeof contrast in the renal papilla. kidney. ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  29. 29. A right-sided abdominal mass, which Bilateral renal angiomyo-lipomasis a renal cell carcinoma in a case of in a case of TSTS. ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  30. 30. Contrast-enhanced axial CT scan abdomen shows cysts within thepancreas and the right kidney. Note also a solid 3 cm lesion (mid pole,right kidney, posterior renal cortex [red arrow]). A further smaller lesionis seen in the renal cortex more anteriorly, which is too small tocharacterize (blue area) in a case of von Hippel-Lindau syndrome . ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  31. 31. Treatment MCDK is not treatable. Regular follow up of infant for the first few years by ultrasounds Nephrectomy of unhealthy kidney is indicated in:  renal hypertension  malignant transformation. Evaluation of contra lateral kidney to rule out vesicoureteric reflux, about 25% (MCUG). ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  32. 32. Treatment ADPKD, Treatment may include: Blood pressure control (ACEI,ARB). MTOR inhibitors show some benefit in limiting in limiting the increase in kidney size but not the decrease in GFR & increase proteinuria Vasopressin receptor antagonist have shown promising result in mice & rat model (via intracellular CAMP) phase 3 trial in progress), Diuretics & Low salt dietESNT-CNE 1st Course Cairo Sept 10-14, 2012
  33. 33. Treatment Treatment of urinary UTI Cysts that are painful, infected, bleeding, or causing a blockage may need to be drained. Surgery to remove one or both kidneys may be needed. Treatments for ESRD (dialysis / kidney transplant).ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  34. 34. HALT PKD is the first large multicenter randamized double blindplacebo control study that evaluate potential benefits of rigorous BPcontrol and inhibition of the renin-angiotensin-aldosterone system onkidney disease progression in ADPKD. Study A: change in the (kidney volume (MRI Study B: time to 50% pts 548 pts 470 4 yrs 4-6 yrs reduction of GFR HALT polycystic kidney disease (PKD) Boehringer ingelheim –Merck PKD Foundation Randomized, double blind, placebo- controlled 2006-2011ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  35. 35. Treatment MCKD, there is no cure for this disease.  Drinking plenty of fluids and take salt supplements to avoid dehydration.  Treatment of hyperuricaemia/gout (allopurinol).  Treatment of CRF includes medications and diet changes, (limiting foods containing phosphorus and potassium).  For those with ESRD need dialysis or a kidney transplant.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  36. 36. Treatment MSK , to reduce the incidence of stones formation in high risk patients. They can include the following:  Thiazide diuretics for hypercalciuria  Potassium citrate or allopurinol for hyperuricosuria  Potassium citrate for hypocitraturia Initial dose of K citrate 20meq/d titrated to urinary citrate 450mg/d. Increasing fluid, reducing salt and protein intake.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  37. 37. Treatment of VHL VEGF inhibitors, sorafenib and sunitinib FDA approval. Rapamycin may also be an option. Bevacizumab, a monoclonal antibody targeting VEGF, is under clinical trials Iron, 2-oxoglutarate and oxygen are necessary for the inactivation of HIF, their deficiency reduce the ability of hydroxlases in inactivating HIF. Vitamin C may be a potential treatment for HIF induced tumorsESNT-CNE 1 Course Cairo Sept 10-14, 2012 st
  38. 38. Treatment of TSC ? Rapamycin decrease the size of mass of angiomyolipomas by 50% ( as it is associated with phosphorylaton by MTORs). Bilateral nephrectomy before renal transplantation (as there is increase risk of RCC by immunosupression.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  39. 39. ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  40. 40. References1-Amoroso. Autosomal dominant medullary cystic kidney disease with or without hyperuricemia. Orphanet. June 2006.2-Avner ED, Sweeney WE. Renal cystic disease: new insights for the clinician. Pediatr Clin North Am. Oct 2006;53(5):889-909,3-Bisceglia M, Galliani CA, Senger C, Stallone C, Sessa A. Renal cystic diseases: a review. Adv Anat Pathol. Jan 2006;13(1):26-564-Bonsib M.S.,2009 renal cystic disease & renal neoplasm journal: clinical journal of the American society of nephrology, CLIN.J.AM.SOC. Vol.4.(12) pp 1998-2007.5-Choyke PL. Acquired cystic kidney disease. Eur Radiol. 2000;10(11):MF, Meller J 2004. "von Hippel–Lindau tumor 1716-21.Curry, Nancy SCochran, et al., 2000: cystic renal masses , accurate Bosniak classification reqiure accurate CT Am. J. Roentgnol, 175-339-432.6-Czyzyk-Krzeska suppressor: not only HIFs executioner". Trends in molecular medicine (4): 146–9.7-Gunay-Aygun M, Avner ED, Bacallao RL, Choyke PL, Flynn JT, Germino GG, et al. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis: summary statement of a first National Institutes of Health/Office of Rare Diseases conference. J Pediatr. Aug 2006;149(2):159-64.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  41. 41. References8-Guay-Woodford LM. Renal cystic diseases: diverse phenotypes converge on the cilium/centrosome complex. Pediatr Nephrol. Oct 2006;21(10):1369-76.9-Kaelin, WG (2004). "The von Hippel–Lindau Tumor Suppressor Gene and Kidney Cancer". Clinical Cancer Research 10 (18 Pt 2): 6290s–6295s10-Kalyoussef E, Hwang J, Prasad V, Barone J. Segmental multicystic dysplastic kidney in children. Urology. Nov 2006;68(5):1121.e9-11.11-Knowles HJ, Raval RR, Harris AL, Ratcliffe, PJ. (2003). "Effect of ascorbate on the activity of hypoxia-inducible factor in cancer cells". Cancer Research 63 (8): 1764–8.12-Saunier S, Salomon R, Antignac C. Nephronophthisis. Curr Opin Genet Dev. Jun 2005;15(3):324-3113-Thomsen HS, Levine E, Meilstrup JW, Van Slyke MA, Edgar KA, Barth JC, et al. Renal cystic diseases. Eur Radiol. 1997;7(8):1267-75.ESNT-CNE 1st Course Cairo Sept 10-14, 2012
  42. 42. Important abbreviationAC= adenyl cyclaseAMP= adenosine mono phosphateATP= adenosine triphosphateCDK= Cyclin dependant kinaseCFTR= cystic fibrosis transmembrane conductor regulatorER= endoplasmic reticulumErbB= epidermal growth factor receptorJAK= Janus kinaseMTOR= Mammalian target of rapamycinRheb= Ras homolog enriched in brainV2R= vasopressor 2 receptorPC1= polycystin 1PC2= polycystin 2PDE=phosphodiesterasePKA= protein kinaseSTAT= Signals transducer & a Activator s of transcriptionTSC1= tuberous sclerosis complex 1TSC2= tuberous sclerosis complex 2ESNT-CNE 1st Course Cairo Sept 10-14, 2012
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