Renal manifestations of ADPKD R 1 Introduction ADPKD

Renal manifestations of ADPKD 신장내과 R 1 최경진

Introduction - 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

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 ( > 15 cm in length) § Hypertension § Higher plasma creatinine concentrations § Association with worse renal outcomes

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

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

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

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

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( < 2 cm in diameter) is successful § Percutaneous nephrolithotomy in a limited patients

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

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

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

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

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(+)

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)

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

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

Urinary tract infection § Large infected cysts(>3~5 cm) § 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

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 § §