1. Renal manifestations of ADPKD 신장내과 R1 최경진

2. Introduction - ADPKD  ADPKD  Continued enlargement of the cysts  Leads to progressive renal failure  Total kidney volume is the strongest predictor for the development of renal insufficiency  Renal manifestation of ADPKD  Hypertension / Urinary tract infection / Hematuria  Concentrating defect / Nephrolithiasis  Acute or chronic flank & Abdominal pain  All complications relate directly to the extent of renal cyst involvement : be assessed by total kidney volume measurements

3. Hematuria  Occurs in 35-40% of Pt. with ADPKD  Usually occurs prior to loss of kidney function  May be presenting symptom of the disease  Gross hematuria is associated with more rapid progression of kidney disease in ADPKD  Gross hematuria is more likely in  Larger kidneys ( > 15cm in length)  Hypertension  Higher plasma creatinine concentrations  Association with worse renal outcomes

4. Hematuria  Rupture of a cyst into the collecting system  Be responsible for the development of hematuria  Although hemorrhage into a cyst is common, typical presentation is pain d/t many cysts don’t communicate with the collecting system  Hematuria resolves within 2-7 days with conservative therapy : Bed rest, Hydration, Analgesics not NSAID  Unusual & severe bleeding  Percutaneous arterial embolization  Nephrectomy

5. Concentrating defect  Complain of thirst, polyuria, nocturia & urinary frequency  a Decrease in urinary concentrating ability is one of the earliest manifestations of ADPKD  Worsens with increasing age & declining kidney function  Severity of anatomical deformities induced by the cysts  Underlying cause is not known  Disruption of tubular architecture  Defect in principal cell function  Early tubulointerstitial disease

6. Concentrating defect  Elevation of Vasopression level > Central cause is excluded  occurs early in the course of the disease  in order to preserve water balance  Urine diluting capacity appears to be intact in ADPKD  Increased vasopressin concentration may play a role in disease progression  Strategies to inhibit vasopressin action are potential therapeutic modalities in ADPKD  Vasopressin Rc antagonists  reduce vasopressin levels with increased free water intake

7. Nephrolithiasis  Occurs in -25% of Pt. with ADPKD  Composition of uric acid > ½ of stones in ADPKD  Risk factor for nephrolithiasis  Increased renal volume : controversial  In one study, renal volume determined by CT was greater in 35 pts with ADPKD and nephrolithiasis, compared with those who had ADPKD but no nephrolithiasis  In the CRISP study of 241 individuals, no association between nephrolithiasis and kidney volume could be established  Low urinary volume / Low urinary citrate  Hyperuricosuria / Hypercalciuria

8. Nephrolithiasis  Diagnosis of stone  by USG is more difficult than in idiopathic stone formers,  the large cysts obscuring the view of the collecting system  calcifications that may be present in the cyst walls  Most stones can be detected by Intravenous pyelography  By CT scanning is more sensitive for small or radiolucent stones  Treatment of obstructing stones  More difficult than idiopathic stone disease  Cystoscopy : be complicated by an infected cyst  Percutaneous nephrostomy or ESWL is hard d/t large cysts  small stones( < 2cm in diameter) is successful  Percutaneous nephrolithotomy in a limited patients

9. Flank & Abdominal pain  Common problem  Can be due to renal or extrarenal etiologies  Acute kidney pain  Infections (cystic or parenchymal)  Nephrolithiasis  Cyst hemorrhage  Cysts in the liver  Chronic kidney pain  more common in advanced disease who have enlarged kidneys  Dull, persistent  Stretching of the capsule or traction on the renal pedicle

10. Renal cell carcinoma (RCC)  an infrequent complication of ADPKD  not occur with increased frequency than general population  Differentiating characteristics of RCC in ADPKD  Patients frequently present with fever  Bilateral at presentation  Multicentric  Sarcomatoid type

11. Renal cell carcinoma (RCC)  Diagnosis of RCC is difficult in ADPKD  Hematuria / a Flank mass / Bleeding into cysts / a Complex cyst on USG, CT or MRI > common in ADPKD with out malignancy  Some clinical clues may be helpful  systemic signs & symptoms( fever, anorexia, fatigue, Wt.loss)  rapid growth of a complex cyst  Percutaneous aspiration & cytologic examination

12. Urinary tract infection  Approximately 30–50 % of patients with ADPKD  An infected cyst & APN = m/c kidney infections  Cyst infection incidence = 0.01 episode/patient /year  Source of infection  Women > Men  Typically caused by Gram(-) enteric organisms  the causes of cyst infection are often more difficult to document  the cysts may not be in communication with the collecting system  the urine culture is often negative  20 % of patients with ADPKD develop nephrolithiasis, a source of recurrent infections

13. Urinary tract infection  Clinical features  Fever / Flank pain / Nausea / Vomiting  A more insidious presentation  Location of the cyst infection > specific area of tenderness  Diagnosis  Pyelonephritis : Diffuse flank pain / urine culture(+) / blood culture(+)  Infected cyst : Discrete Td / urine culture(-) / blood culture(+)

14. Urinary tract infection – Antibiotics  whether the patient has PN or a cyst infection, it is frequently difficult to initially distinguish between the two the Choice of initial empiric therapy : to successfully treat both types of infection  Therapeutic concentrations within cysts + against Gram(-) enteric organisms  Ciprofloxacin  Levofloxacin  Trimethoprim-sulfamethoxazole  Chloramphenicol  No penicillins (do not penetrate the cyst)

15. Urinary tract infection – Antibiotics  Initially with intravenous Ciprofloxacin  Initially with Cefotaxime or Ampicillin + Gentamycin, because Quinolone resistance is an increasing problem  Streptococcal or staphylococcal infection  Vancomycin or erythromycin  Resistant group A streptococcal infection  Levofloxacin  Anaerobic organism  Metronidazole or Clindamycin

16. Urinary tract infection – Antibiotics  The duration of therapy  APN : a minimum of 10~14 days  Optimal duration of therapy for infected cysts is unclear  for at least 4 weeks and sometimes for up to 6 weeks  If the infection recurs after withdrawal of antimicrobials, therapy may be reinstituted and continued for 2~3 months or longer

17. Urinary tract infection  Large infected cysts(>3~5cm)  are more likely to fail medical therapy  Percutaneous or surgical drainage of the cyst  Infrequently necessary & hard to perform  Difficult to ascertain radiologically which of the many cysts is infected  Perinephric abscess  Drainage may be indicated  Recurrent UTIs  Stone removal procedures may be required if nephrolithiasis is contributing to recurrent UTIs

18. Nephrectomy in ADPKD  though Cyst formation occur < 5-10% of nephrons  Cyst and total renal size increase progressively over time  Unilateral or Bilateral nephrectomy indication  Recurrent infection  Limitation of daily activities, fatigue, & anorexia (signs of malnutrition)  Suspected malignancy  Extension of the native polycystic kidney into the potential pelvic surgical site.  Uncontrollable renal hemorrhage in CIx to or failure of intraarterial embolization  Development of ventral hernia d/t massive renomegaly