6 курс / Нефрология / Острое_повреждение_почек_после_паратиреоидэктомии_по_поводу_первичного
.pdf221
3.2.2. Initial kidney status related factors
One of the most significant AKI risk factors in the general population is preexisting CKD, thus to assess the disease prevalence in the study sample was of particular interest. It should be noted CKD stage 1 and 2 is rarely diagnosed in general therapeutic practice but rather is in the scope of specialized nephrology centers, and is mainly applied to the patients with a morphologically confirmed chronic glomerulonephritis without renal function impairment, as an isolated form or as a systemic pathology. Patients with PHPT are routinely managed by an endocrinologist and, if necessary, a physician, and CKD diagnosis is most often established in them based on persistent GFR decrease of less than 60 mL/min/1.73 m2 - i.e., CKD stage C3 and above. In the study population, 19 of 106 patients with AKI (17.9%) and in 22 of 184 patients without AKI (12%) was aggravated with pre-existent CKD.
The risk of AKI did not differ in patients with and without baseline CKD: RR=1.33 [95%CI 0.88; 1.86], OR=1.6 [95%CI 0.82; 3.04], p=0.1601. There was also no statistically significant association of AKI risk and pre-existing CKD (p=0.451).
The median eGFR in patient groups with and without AKI was 84.45 mL/min/1.73 m2 [Q1-Q3: 65,5; 96.6] and 76.6 mL/min/1.73 m2 [Q1-Q3: 64.9; 90.6] respectively, p = 0.118. The ROC curve was obtained to assess eGFR impact on AKI probability (Figure 3.19). The area under the obtained eGFR ROC curve was 0.555 [95%CI 0.48; 0.63], p=0.1179.
For a more detailed analysis of baseline eGFR and AKI association, the patients were divided into subgroups depending on the eGFR: of more than 60 mL/min/1.73 m2 group and of less than 60 mL/min/1.73 m2 group. No statistically significant difference was shown for AKI incidence in patient groups of different baseline eGFR (p =0.4656) - Figure 3.7. Thus, patients with both preserved and reduced eGFR are at equal risk of postoperative AKI.
Рекомендовано к изучению сайтом МедУнивер - https://meduniver.com/
222
n of observations
≥60 <60 eGFR, ml/min/1,73 m2
AKI
No AKI
Figure 3.7. AKI incidence in patient groups of different baseline eGFR.
Proteinuria is a reliable marker of pre-existing renal injury and its extent. Preoperative urinalysis results were available in 239 of 290 patients in the study population. Proteinuria was observed significantly more often in patients with AKI compared to patients without AKI: 17% (15/88) vs 5.3% (8/151) respectively – Figure 3.8. The risk of AKI was significantly higher in patients with protein in the urine: RR = 1.9 [95% CI 1.19; 3.54], OR=3.67 [95%CI 1.5; 8.73], p=0.0061. Only 5 of 23 (21.7%) patients with proteinuria had eGFR of less than 60 mL/min/1.73m2.
Χ2 (Yates’ correction) |
AKI |
|
|
|
No AKI |
n of observations
yes no Proteinuria
Figure 3.8. AKI incidence depending on concomitant proteinuria.
One of the important AKI risk factors for is intraoperative hypotension. Since hemodynamics is most variable during the patient’s mechanical ventilation,
223
intraoperative blood pressure dynamics analysis was reasonably limited by this time period. The median ventilation duration was 45 minutes [Q1-Q3: 35; 60]. The incidence of IOH, defined as the average blood pressure of less than 65 mm Hg, was small, which is due to the minimally invasive surgery performed and the relatively short intervention duration. In the AKI patient group IOH was observed in 5.7% (6/106) of cases, in patients without AKI - in 4.9% (9/184) of cases; observed IOH did not affect AKI risk (RR = 1.1 [95%CI 0.5; 1.8], OR = 1.17 [95%CI 0.4; 3.2], p =0.79). The duration of hypotension was also small - the median time was 10 minutes [Q1-Q3: 10; 15]. No statistically significant difference was observed for the minimal MBP in the AKI patient group compared to those without AKI: 72 mm Hg [Q1-Q3: 68; 78] vs 73 mm Hg [Q1-Q3: 70; 78], p = 0.33. The intervention duration was comparable in AKI patient group and no AKI patient group (30 min [Q1-Q3: 20; 45] vs 25 min [Q1-Q3: 20; 35], p = 0.409).
3.2.3. PHPT related factors
From the analysis of AKI risk and pre-operative PTH level association the median PTH concentration in AKI patients was found to be significantly higher compared to that of the patients without AKI: 17.75 pmol/L [Q1-Q3: 12; 24.2] vs 13.8 pmol/L [Q1-Q3: 10.2; 19.6] respectively, p = 0.0004 (Figure 3.9). The ROC curve was obtained to assess preoperative PTH level impact on AKI probabilityFigure 3.20. The area under the obtained PTH level ROC curve was 0.625 [95%CI 0.56; 0.69], p = 0.0004. The PTH level cut-off point was 16.95 pmol/L. With the selected cut-off point, the Se was 0.679 [95% CI 0.61; 0.74], the Sp - 0.557 [95%CI 0.46; 0.65], SBA was 0.618, p<0.0001. Patients with baseline PTH levels greater than 16.95 pmol/L have a higher risk of AKI: RR=1.45 [95%CI 1.2; 1.8], OR=2.66 [95%CI 1.62; 4.3].
Рекомендовано к изучению сайтом МедУнивер - https://meduniver.com/
224
|
|
|
PTH, pmol/l |
|
ΔPTH, pmol/l |
|
|
|
|
|
|
yes |
no |
yes |
no |
|
AKI |
|
AKI |
|
|
|
|
Figure 3.9. Pre-operative PTH level (left) and before/after surgery PTH level difference (right) in patient groups with and without AKI (the Mann-Whitney test). The medians, the first and third quartiles are given, the shape of the figures reflects the variable distribution.
High PTH levels were naturally observed in patients with removed PTG of a large volume (ρ=0.353 [95%CI 0.25; 0.45], p<0.0001), as well as with adenoma of a high weight (ρ=0.505 [95%CI 0.37; 0.62], p<0.0001) and of greater maximum linear size
(ρ=0.353 [95%CI 0.24; 0.45], p<0.0001). All these parameters of the disease severity and duration, are closely related: statistically significant direct high correlations were established in the study for removed PTG volume and weight (ρ=0.866 [95%CI 0.82;
0.9], p<0.0001), volume and maximum linear size (ρ=0.896 [95%CI 0.87; 0.92], p<0.0001) and weight and maximum linear size (ρ = 0.855 [95%CI 0.8; 0.9], p<0,0001).
(Figure 3.10)
225
units (see graph legend)
Adenoma size, mm
Adenoma weight, g
Adenoma volume, sm3
Figure 3.10. Parathyroid adenoma size, weight and volume correlations with Spearman's test. Linear correlation estimation is given, the points indicate 95%CI.
Adenoma maximum size is of the greatest interest for the routine practice, since it cannot be easily detected by ultrasonography or CT. In AKI patients, the median parathyroid adenoma maximum size was greater than that of the patients without AKI: 20 mm [Q1-Q3: 10; 25] vs 15 mm [Q1-Q3: 10; 20] respectively, p= 0.0184 (Figure 3.11). The ROC curve was obtained to assess the parathyroid adenoma maximum size impact on the AKI probability - Figure 3.20. The area under the obtained parathyroid size ROC curve was 0.582 [95%CI 0.51; 0.65], p = 0.02. The adenoma maximum size cut-off point was 16.5 mm. With the selected cut-off the Se was 0.628 [95% CI 0.56; 0.7], the Sp – 0.547 [95%CI 0.45; 0.64], SBA – 0.588, p=0.0037. With an initial adenoma size of greater than 16.5 mm, the risk of AKI increased: RR=1.31 [95%CI 1.09; 1.59], OR=2.04 [95%CI 1.26; 2.6].
Рекомендовано к изучению сайтом МедУнивер - https://meduniver.com/
226
Adenoma size, mm
yes no AKI
Figure 3.11. Parathyroid adenoma maximum linear size in patient groups (with and without AKI) comparison with the Mann-Whitney test. The medians, the first and third quartiles are given, the shape of the figures reflects the variable distribution.
PTx resulted in a PTH levels decrease on day 1 post-surgery from 14.8 pmol/L [Q1- Q3: 10.7; 21.5] to 1.7 pmol/L [Q1-Q3: 0.9; 3.3], p<0.0001 - Figure 3.12. Preoperative PTH level and the decrease extent (ΔPTH) correlated strongly: ρ=0.96 [95%CI 0.95; 0.97], p<0.0001. High values of the before/after surgery PTH level difference were associated with the risk of AKI: median ΔPTH in patients with AKI was 16.7 pmol/L [Q1-Q3: 10; 23] vs 11.35 pmol/L [Q1-Q3: 7.4; 17] in patients without AKI, p<0.0001 (Figure 3.9). The ROC curve was obtained to assess ΔPTH impact on the AKI probability - Figure
3.20. The area under the obtained ΔPTH ROC curve was 0.64 [95%CI 0.57; 0, 71], p<0.0001. The ΔPTH cut-off point was 15.55 pmol/L. With the selected cut-off point, the Se was 0.712 [95%CI 0.64; 0.77], the Sp was 0.528 [95%CI 0.43; 0.62], SBA was 0.62, p<0.0001. Patients with ΔPTH greater than 15.55 pmol/L had a higher risk of AKI:
RR=1.49 [95%CI 1.22; 1.86], OR=2.77 [95%CI 1.67; 4.53].
227
PTH, pmol/l
Before After surgery surgery
Figure 3.12. Post-PTx PTH level dynamics with the Wilcoxon test. The medians, the first and third quartiles are given, the shape of the figures reflects the variable distribution.
Patients with high PTH levels had higher preoperative levels of both total (ρ=0.509 [95%CI 0.36; 0.63], p<0.0001) and ionized calcium (ρ=0.432 [95%CI 0.33; 0.52], p<0.0001) - Figure 3.13. With this, the total calcium level was closely correlated with pre-PTx PTH level compared to ionized calcium level, – р=0.0134.
units (see graph legend)
PTH, pmol/l
Total serum Ca, mmol/l
Ionized serum Ca, mmol/l
Figure 3.13. Preoperative total and ionized calcium level correlations with PTH level with Spearman's test. The linear relationship estimation is provided, the points indicate 95% CI.
The mean total serum calcium level pre-operatively was slightly higher in AKI patient group: 2.83±0.29 mmol/L vs 2.71±0.22 mmol/L in the group of patients without
Рекомендовано к изучению сайтом МедУнивер - https://meduniver.com/
228
AKI, the difference was statistically significant (p = 0.0158) - Figure 3.14. The mean difference was 0.113 mmol/L [95%CI 0.02; 0.2]. The ROC curve was obtained to assess the total calcium level impact on the AKI probability - Figure 3.20. The area under the obtained total calcium level ROC curve was 0.616 [95%CI 0.51; 0.72], p=0.0292. Total calcium level cut-off point was 2.83 pmol/L. With the selected cut-off point, the Se was 0.754 [95%CI 0.64; 0.84], the Sp was 0.481 [95%CI 0.35; 0.61], SBA was 0.618, p=0.0073. With a preoperative total calcium level of greater than 2.83 mmol/L, the risk of AKI increased: RR=1.63 [95%CI 1.13; 2.5], OR=2.83 [95%CI 1.33; 5.9].
Total serum Ca, mmol/l |
|
|
|
Ionized serum Ca, mmol/l |
|
|
||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
yes |
no |
|
|
|
yes |
no |
|
|
|
AKI |
|
|
|
|
AKI |
|
|
|
|
|
|
|
|
|
Figure 3.14. Left: total calcium levels in patient groups (with and without AKI) comparison with the Student's t-test. The distribution, means, means standard deviations are given. Right: ionized calcium levels in patient groups (with and without AKI) comparison with the Mann-Whitney test. The distribution, medians, and interquartile ranges are given.
Statistically significant difference was demonstrated for AKI incidence in the patient groups with different preoperative total serum calcium levels according to the National Recommendations for PHPT Diagnosis and Treatment of PHPT [1] (mild hypercalcemia - total calcium level of less than 3.0 mmol/L, moderate/severe hypercalcemia - 3.0 mmol/L or more). The total proportion of patients with moderate to severe hypercalcemia was higher among patients with AKI compared to those without
229
AKI: 25% (13/52) vs 7.25% (7/69), respectively. Moderate/severe hypercalcemia had a statistically significant impact on the AKI risk: RR=1.91 [95%CI 1.22; 2.69], OR=4.28 [95%CI 1.39; 11.38], p=0.0092 - Figure 3.15.
Fischer’s exact |
AKI |
|
test |
||
|
||
|
No AKI |
|
|
n of observations
mild moderate+severe
Hypercalcemia
Figure 3.15. AKI incidence in patient groups with different preoperative total serum calcium levels.
No statistically significant difference was demonstrated in the median ionized calcium levels of AKI patients compared to those without AKI (1.47 mmol/L [Q1-Q3: 1.35; 1.54] vs 1.45 mmol/L [Q1-Q3: 1.36; 1.55] respectively, p=0.496) - Figure 3.14.
PTx led to ionized blood calcium level decrease on day 1 from 1.45 mmol/L [Q1- Q3: 1.35; 1.55, from 1.15 to 2.23] to 1.23 mmol/L [Q1-Q3: 1.16; 1.31, from 0.88 to 1.86], p<0.0001. However, no statistically significant association was demonstrated for ionized calcium decrease extent impact on the AKI probability (p = 0.3706). – Figure 3.16
Рекомендовано к изучению сайтом МедУнивер - https://meduniver.com/
230
|
|
|
∆ Ionized serum Ca, mmol/l |
|
|
|
||
Ionized serum Ca, mmol/l |
|
|
|
|||||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
yes |
no |
|
|
Before |
|
|
|
|
||
|
|
After |
|
|
|
|||
|
|
|
|
|
|
AKI |
||
|
|
surgery |
surgery |
|
|
|
|
|
|
|
|
|
|
|
|
||
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Figure 3.16. Left: post-PTx Ca2+ level dynamics (Wilcoxon test). The medians, the first and the third quartiles are given, the shape of the figures reflects the variable distribution. Right: before/after PTx Ca2+ level difference in patient groups with and without AKI (Mann-Whitney test). The distributions, medians, and interquartile ranges are given.
Long-lasting PHPT leads to target organs damage, the main of which are kidneys, skeleton, gastrointestinal tract. Bone and/or visceral disease manifestations are the absolute indications for surgical treatment. In this regard, the most common organ damages incidence associated with PHPT was analyzed in the study, as well as their relationship with the key laboratory parameters and the impact on the AKI risk.
Kidneys are one of the main target organs in PHPT: elevated PTH levels lead to hypercalciuria and nephrolithiasis in patients. The kidney stones were naturally observed in more than half of patients (56.9%, 165 out of 290) in the study population. Patients with higher PTH levels experienced urolithiasis: the median PTH levels in patient groups with and without AKI were 15.5 pmol/L [Q1-Q3: 11.5; 21.95] and 13.8 pmol/L [Q1-Q3: 9.8; 19.3] respectively, p=0.0308. The PTH level median difference was 1.9 pmol/L [95%CI 0.2; 3.6]. At the same time, no association of urolithiasis with total and ionized calcium levels was noted (p=0.97, p=0.1138 respectively). Nephrolithiasis was observed in 65 patients with AKI (61.3%) and 100 patients without AKI (54.4%). However, the