NON - GLOMERULAR DISEASES  diagnosis is done before the onset of symptoms, when
(Dr. Lu online class, 2020) members of the family request for screening
Non glomerular Hematuria
What differentiates is the size and shape of the RBC. If the patient presents
with hematuria, dividie it into glomerular and non-glomerular via looking
under the microscope.
Cystic diseases of the kidney
POLYCYSTIC KIDNEY DISEASE
I. Autosomal Dominant Polycystic Kidney disease
 systemic disorder, predominantly in adult
 mutations in either PKD-1 or PKD-2 gene
 polycystein-1(encoded by PKD-1) is a large receptor-like
molecule
 polycystein-2 has a feature of a calcium channel protein
 transmembrane protein present throughout all nephron
segments
 regulate fetal and adult epithelial cell gene transcription,
apoptosis, differentiation and cell-matrix interactions
Transmembrane proteins are seen in the following areas:
1. Luminal surface of tubular cells in primary cilia (flow sensors)
2. Basal surfaces in focal adhesion complexes
3. Lateral surface in adherens junction
 vasopressin mediated elevation of cAMP levels in cyst
epithelia plays a major role in cystogenesis by stimulating
cell proliferation and fluid secretion into the cyst lumen
through apical chloride and aquaporin channel
 cyst formation began in utero and < 5% of total nephron are
involved
 as the cysts accumulate fluids, they enlarge and separate
from the nephron, compress the neighboring renal
parenchyma and progressively compromise renal function
The cyst as it enlarges, it compresses the neighboring cyst. It will destroy the
renal parenchyma at compromise the renal function. The kidney will become
very big (16-18 cm), that is filled up with cyst at the cortex or medulla. In
ADPKD, the cyst can be located at the cortex and medulla.
 occurs 1: 400 - 1: 1,000 worldwide
The number one cause of dialysis is diabetic nephropathy, followed by chronic
hypertension and third is only glomerular pathology. Fourth one is the tubula r
diseases, one of those is ADPKD
 4% ESRD in USA
 inherited as autosomal dominant trait, the rest spontaneous
mutation
 mutation in PKD-1 gene on chromosome 16p13 (ADPKD-1):
85% of cases
 PKD-2 gene on chromosome 4q21 (ADPKD-2), later onset and
slower progression
 phenotypic heterogeneity - hallmark, the same mutation but
different clinical course
 both cortex and medulla are involved
Ultrasound is the best diagnostic procedure for looking at the kidney
structure.
 often asymptomatic into the 4 th or 5 th decade
 symptoms: abdominal discomfort, hematuria, UTI, incidental
discovery of HPN, abdominal mass, elevated Scr, cystic
kidneys in imaging
It is often asymptomatic except hypertension. Symptoms are usually caused
by the compression of the cyst. It can manifest as systemic, because it
involves other organ system. One of them is the liver. The liver is also filled
up with cyst.
 renal function progressively declines over 10-20 years from
the time of diagnosis
 not everyone with ADPKD develops ESRD, 60% of these
patients by age 70
 HPN is common, often precedes renal dysfunction, mediated
via increased activity of RAAS
 mild proteinuria, impaired urinary concentrating ability
(polyuria and nocturia)
 risk factors for progressive renal disease:
 close correlation between the rate of kidney expansion
(measured by MRI) and rate of decline in renal function
 Younger age at dx, black race, male sex, presence of
polycystein-1 mutation and HPN
First is you request urinalysis as the basic diagnostic tool in nephrology. In
order to know if the patient has two kidneys, you have to do imaging. So you
need to use KUB (kidney ultrasound). Then go to your history and PE. Including
the blood pressure.
 dull, persistent flank and abdominal pain and early satiety
 sudden abdominal pain/localized peritonitis: cyst rupture and
hemorrhage into the cyst
 gross hematuria: cyst rupture into collecting system or from
uric acid or calcium oxalate stone (20% nephrolithiasis)
 UTI, acute pyelonephritis-increased in frequency, pyocyst
(Gram negative) is a serious complication
The color of the urine is bright red. If it is bright red, it is most likely non-
glomerular. When you talk about coca cola colored, or tea or rusty colored,
this is the characteristic of glomerular hematuria.
Extrarenal manifestations
 2-4x increased risk in subarachnoid/cerebral hemorrhage
from a ruptured intracranial aneurysm
 saccular aneurysm of anterior cerebral circulation (10% in
asymptomatic), majority are small with low risk for
spontaneous rupture
 Risk of hemorrhage: occur before age 50 years, family
history of IC hemorrhage, those who have survived a
previous bleed, aneurysm > 10 mm, uncontrolled HPN
 other vascular abnormality: aortic root and annulus dilation
 cardiac valvular abnormalities (25%)-MVP and AR
 hepatic cyst (83%) age 15-46 yrs (MRI), asymptomatic,
normal liver function, but these may bleed, become infected,
rupture and cause pain, women are more likely to have
massive cysts
 colonic diverticula are common, with higher incidence of
perforation
 abdominal wall and inguinal hernia occur higher frequency
than the general population
Diagnosis
 Dx: - positive family history
- positive imaging procedure
 those 60 y/o and above requires at least 4 or more cysts in
each kidney
 fewer than 2 renal cyst in at risk individuals is sufficient to
exclude the disease
 genetic linkage analysis and mutational screening for ADPKD-
1 and ADPKD-2
 CT scan and T2 weighted MRI for equivocal
 screening for asymptomatic intracranial aneurysm:
 History of IC bleed, high risk occupation
 Intervention aneurysm > 10 mm
 Clinical Presentation
 Hematuria (isomorphic), abdominal pain and flank or
abdominal mass(triad, 10-20%)
 fever, weight loss, anemia, and a varicocele(L)
 most often detected as incidental finding on a radiograph
(MRI, CT, US)
 an improved in 5 yr survival: due to early detection low stage
tumor and nephron-sparing surgery (partial nephrectomy)
Ultrasound Hepato-renal Cysts
 spectrum of paraneoplastic syndrome: erythrocytosis(3%),
II. Benign Renal Cysts hypercalcemia, Stauffer syndrome (non-metastatic hepatic
 Renal cyst- fluid collection in the kidney dysfunction) and acquired dysfibrinogenemia, HPN, night
 Simple renal cyst: sweats and malaise
1. Observation, no intervention Paraneoplastic syndrome are the reason why patients a reseen by the internist and not
by the surgeon. However, these symptoms are non specific
2. Monitoring
 Up to 27% of individuals > 50y/o may have simple cysts Classic Triad Frequency
causing no symptoms (Clinical Radiology using CT scan) 1. Hematuria 40%
 Worry: cancerous lesions 2. Flank pain 40%
Sometimes you encounter this at the ultrasound report, found as 1 or 2 cyst 3. A palpable mass in 25%
in the cortex. These are probably benign cyst. Some of this cyst can
flank/abdoment
transform into tumor
Simple renal cyst – has no chance to be malignant. No intervention, you just Other signs/symptoms
monitor. 1. Weight loss 33%
2. Fever 20%
Bosniak Classification 3. Hypertension 20%
Category I: (no ff-up , 0% cancer risk)
4. Hypercalcemia 5%
 hairline thin wall w/o septa, calcifications, solid components
5. Night sweats
 does not enhance with contrast, water density 6. Malaise
Category II: (no ff-up, 0-5% cancer risk)
7. Varicocele 2% of males
 few thin septa w/c may contain fine calcifications, or a small
segment of mildly thickened calcification. Includes also
 anemia is a sign of advanced disease
homogenous, high attenuation lesions < 3 cm with sharp
margins BUT w/o enhancement  Evaluation:
Category IIF :(ff-up imaging required, 5-25%) 1. CT scan of abdomen and pelvis
2. CXR
 well marginated cyst with a # of thin septa, with or w/o mild
3. Urine analysis/cytology
enhancement or thickening of septa
4. If metastatic disease is suspected in CXR, do CT of chest
 calcifications maybe present, maybe thick and nodular
5. MRI- to evaluate tumor involvement of IVC or tumor
 No enhancing soft tissue components, also includes non-
invasion by thrombus
enhancing high-attenuation lesions that are completely * any solid renal mass should be considered malignant unless proven otherwise
contained w/in the kidney and are 3 cm or larger
Category III:(surgical treatment, 50-54%) Differential Diagnosis of Renal Mass
 indeterminate cystic masses with thickened irregular septa 1. Renal Cyst
with enhancement (you need to rule out possibility of 2. Benign neoplasm (adenoma, angiomyolipoma, oncocytoma)
malignancy) 3. Inflammatory lesions (pyelonephritis, abscess)
Category IV:(surgical treatment, 75-90%) 4. Other primary or metastatic cancers
 malignant cystic masses with all the characteristics of 5. Less common malignancies involving the kidneys: transitional
category III lesions BUT also with enhancing soft tissue cell carcinoma of renal pelvis, sarcoma, lymphoma and
components independent of but adjacent to the septa Wilm’s tumor
In renal cysts, they have contents. They are fluid containing cysts.
Renal cell carcinoma
 90-95% of malignancy arising from the kidney
 male to female: 2:1
 incidence peak between ages 50-70(mean age)
 Risk factors: cigarette smoking, acquired cystic disease of the
kidney associated with ESRD, tuberous sclerosis, 35% with
VHL(von Hippel-Lindau) develops clear cell RCC
 60% clear cell type, 5-15% papillary tumors(bilateral and
multifocal), 5-10% chromophobic, 5-10 oncocytoma Normal and clear cell type
(benign), <1% collecting duct or Bellini duct tumor(rare but
aggressive)
 clear cell arise from epithelial cells of proximal tubules and
show chromosome 3p deletion


Diagnostic Evaluation

Contrast-enhanced MRI Grey scale ultrasound image LOCALIZED disease

A rounded mass extending off from the posterior kidney
 Radical nephrectomy: large and centrally localized tumors
Management that have replaced the normal renal parenchyma, tumor
 Surgical option for no demonstrable metastasis even if renal associated with regional adenopathy(of benign or malignant
vein is invaded etiology), those with IVC or right atrial extension, or even
those with metastatic disease is evident
METASTATIC disease (30%)
 20-30% resected primary tumors relapsed with metastasis
VARICOCELE

(R) Testicular veinIVC

 Standard management for stage I or II tumors and selected (L) Testicular vein 
cases of stage III disease is radical nephrectomy renal vein IVC
 Involves en bloc removal of Gerota’s fascia and its content
kidney, ipsilateral adrenal gland and adjacent hilar LN. Varicocele develops because the tumor blocks the renal vein. Which is also
Extension to renal vein and IVC (Stage III) does not preclude the drainage of left testicular vein. That is why the veins becomes prominent
resection in left scrotal area. However, in right side, the testicular vein drains at the IVC.
So even if the renal vein is affected by the tumor, there will be no blockage in
 Survival rates: 60-100% for resected nonmetastatic cortical drainage.
tumors, depends also on the mode of presentation, tumor
histology and size, and pathologic state
 20% for stage III, < 5% for Stage IV
 Prognosis declines for most advanced disease
One of the indicator of advance disease is anemia

HISTOLOGIC TYPES
 Prognosis of clear cell is < favorable than papillary RCC
 Chromophobe RCC is the most favorable
 For patient with metastatic disease, 5 clinical features
associate with shorter survival are:
1. Low performance status
2. High LDH
3. Low hemoglobin
4. High calcium
5. Absence of prior nephrectomy

Staging of Renal Cell Ca